Session E: Breast Cancer AGGRESSIVE FACTORS IN BREAST CANCER EVOLUTION Mariano Cherubini, Attilio Cuviello, Gerardo Guarino Universita degli Studi di Trieste. Dipartimento di Scienze Chirurgiche Generah, Anestesiologiche e Medicina Intensiva. UCO: Clmica Chirurgica. Responsabile- Prof. Aldo Leggen Two groups of patients chosen from a breast screening of 4025 cases are examined. One group refers to pahenis at the I stage of breast cancer and another at the IV stage, characterized by neoplastic recurrence Examinations are performed on the state of receptors at the time of the first operation or at the complete surgical excision of the recurrence, determining the receptor measures in f.mol/ml., receptor phenotypes, the oestogenic progestimc ratio and the grading correlated to the oestrogenic positive or negative receptors. The results show a different receptor percentage in recurrence, which although not significant, indicate a minor presence of ER+ PR+, ER- PR-, and an increase of the ER+PR- phenotype. 'llie recurrence appears more frequently when the lesion at the first operation is more advanced and more often if radiotherapy has not been included in the treatment. The histologtcal grade shows, in recurrence, a greater number of indifferentiated cells and a reduction of ER+, indicating a minor target of the most widely used treatments. The oestrogenic progestinic ratio is significantly increased (p < 0 01) in recurrence (12.7) compared to the I stage (4.44) (Fig I). The cause of recurrence is a neoplastic embolism, documented histologicaliy The recurrence doesn't necessarily mean a poor prognosis, because there is a survival rate after two years in 67% of the cases treated. These results show, with widely used methods, the aggressiveness of some breast tumours, which can evolve and have the poorest outlook even for the most complete therapy. ER/PR in the breast cancer stages (I and IV)


Fig 1 REFERENCES 1) DowsettM Improved prognosis for biomarkers in breast cancer Lancet 1998, 351' 1753-1754 2) Chembim M. et al. Analysis of the evolution of operated breast cancer J Chemiother 1997; 9(2): 129-130 3) Roberti N Hystologic Grade as a prognostic factor in breast carcinoma. Cancer 1997; 80(9) 17061707.

A PHASE I - n STUDY OF GEMCITABINE AND VINORELBINE AS SECOND LINE TREATMENT OF PATIENTS WITH METASTATIC BREAST CANCER. Massuno Fanelli1, Alessandro Morabno ', Gianfranco Filippelh : , Stefano Vitale ', Sergio Palmeri . Manuela Tamburo De Bella ' Sara Gilbert! ', Francesco Ferrau *, Bruno Massida', Stefano Cascinu'. Vincenzo Catalano and Giampietro Gasparim'. Division of Medical Oncology, Azienda Ospedaliera Bianchi-Melacrino-Morelli" of Reggio Calabria. 2 ASL1, Paola. Universita degli studi di Palermo, * Ospedale in Contrada Sirina. Taormina. Universita degli studi di Cagltari, Universita degli studi di Messina. Ospedale S Salvatore, Pesaro. Purpose : To determine the maximum tolerated dose (MTD) of Gemcitabine (G) in combination with Vinorelbine (V) as second line therapy in patients affected by metastatic breast cancer; to evaluate the therapeutic activity and the toxicity of the combination of Gemcitabine and Vinorelbine. Patients and Methods : Eligibility criteria included metastatic breast cancer, measurable or evaluable disease, anthracycline or taxane-based chemotherapy as first-line for melastatic disease, age III non hematological toxicity, except grade 3 alopecia. If at a given dose one patient experienced DLT, 3 additional patients were treated at that dose level. If an additional patients experienced a DLT, no further dose escalation was allowed and that dose level tested was considered as the maximum tolerated dose (MTD). The dose level before MTD is the reccomended dose for the phase II study Results' Nine patients (60 yean, medium age) entered the phase 1 study. Three patients were treated at dose level 1 (G 800 mg/m2) without significant toxicity The MTD was found at the dose level II (G 1000 mg/m2) with 2 patients whoexperienced grade 4 neutropenia. Other toxicities at this dose level were, grade 3 neutropenia (4 patients), grade 2 diarrhea (1 patient) and grade 1 fiebitis (3 patients). Among the25 patients enrolled in the phase II study, 17 are evaluable for the response. No complete response was obseved, 7 patients had partial response (41.2%), 4 stable disease (23.5%) and 6 progressive disease (35.3%). To date, no significant toxicity (grade3 neutropenia in 2 patients) was found. JT 2

Conclusions: The reccomended dose of Gemcitabine is 800 mg/m2 in combination with Vinorelbine 25 mg/m2 on day 1 and 8 The recruitment of the patients for phase II study is ongoing




Daniela Turchetti', Giulio Rossi2, Laura Cortesi3, Chiara Casarini1, Lucia Mangone', Sergio Ferrari3, Gian Paolo Trentini2, Massimo Federico1, Vittono Silingardi 1 'Cattedra e Divisione di Oncologia Medica, Pohchnico di Modena, aCattedra e Servizio di Anatomia Patologica, Policlinico di Modena, 3Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Universita di Modena e Reggia Emilia There is increasing evidence that bread cancers occurring in carriers of BRCAI mutations display specific bio-pathological features, being frequently characterised by a high grade, a high proliferation rate and lack of hormone receptors. In addition, recent data suggest that they are likely to be c-erbB-2-negative and to overexpress p53 Nevertheless, most of the studies so far performed analysed extremely homogeneous populations with regard to ethnical background or age, while, to our knowledge, few data are to date available on the Italian population. In our experience, among individuals undergoing genetic testing because of a strong family history or an early disease onset; the rate of BRCAI mutation carriers was significantly higher in the individuals diagnosed with high grade, high proliferation rate and hormone receptor-negative breast cancers, in comparison to the others (Cortesi et al., 2000). In order to assess the difference between sporadic tumours and BRCAI-associated breast cancers, the immunophenotype of 100 consecutive breast cancer cases was revised and compared to that of 12 breast cancers diagnosed in BRCAl-mutation carriers. Oestrogen Receptors were lacking in 24% of sporadic cancers (SC) and in 82% of BRCAl-associated cancers (BAC) (p paclitaxel regimen seems to be a suitable strategy for MBC treatment. In fact, sequentially administering non-cross-resistant drugs avoids the cumulative hematologic toxicity of their combination and seems to allow a similar antifumor effect.



Orazio Caffo, Maurizio Amichetti, Sonia Brugnara, Francesco Valduga, Antonio Lucenti, Enzo Galltgioni Oncology Department - S. Chiara Hospital - Trento - Italy Introduction: Surgery for BC can alter the women's body image perception and, consequently, the different surgical options can influence the postoperative adjustment of the patients also in terms of sexuality. The present report is aimed to assess the sexuality of women treated for BC with different surgical techniques. Material and methods: We used a multidimensional self-completed questionnaire oriented to assess patients' quality of life, which included the Sexual Activity Questionnaire [SAQ] (Qual. Life Res 5' 81; 1996). The questionnaires were mailed to a consecutive series of women treated between 1995 and 1998 with radical mastectomy [RM] (183 patients), with RM and immediate breast reconstruction fJBR] (80 patients) or with quadrantectomy (QUA) followed by radiotherapy (402 patients). Results and discussion: To date, 471 questionnaires (71%) were returned (126 RM, 55 IBR, 290 QUA). The median age of the women was 60 years (range 33-86). SAQ was compiled by 95% of the pts; 47 % of the women declared to be sexually active. One hundred twenty-three patients (59%) declared to have had three or more intercourse in the last month. The degree of satisfaction concerning the sexual life and the intercourse frequency was high in 147 (70%) patients and 154 (74%) patients respectively, while the post-intercourse satisfaction was high in 167 (80%) women. The value of sexuality in the women's life was considered as high by 116 (55%) of the sexually active women. The comparison of the SAQ answers between the three treatment groups did not show any statistically significant difference. Conclusion: Sexual adaptation after BC surgery can be influenced by several factors, as age, type of surgery or pre-treatment sexual behaviour. Despite this, our preliminary data did not show any difference in sexuality of patients treated with different surgical approaches.



PROGNOSTIC SIGNIFICANCE OF PS3 MUTATIONS IN HIGH RISK NODE POSITIVE BREAST CANCER PATIENTS. K. Cannita, E. Ricevuto, F. De Galitiis, Z.C. Di Rocco, A. Tessitore, G. Porzio, C. Ficorella and P. Marchetti. Department of Experimental Medicine, University of L'Aquila, L'Aquila.

Breast cancer is a genetic disease; several genetic alterations characterize breast cancer and p53 mutations represent the most frequently detected (30%). During the paste decade, many new predictors of outcome have been reported and are evaluated, for their prognostic value, to identify patients at different risk of recurrence (p53, HER-2 neu, bcl-2, BRCA1) P53 mutauons are associated with worse prognosis and with potentially chemio/radioresistance due to inability to trigger programmed cell death. Stromal contaminating normal cells decrease the accuracy of diagnostic technologies for detection of gene mutations in sporadic tumors (SSCP, DGGE, Sequencing Analysis). In our study, molecular scanning of the p53 gene was performed by F.A.M.A (Fluorescent assisted mismatch analysis) in 53 breast cancer patients. F.A.M.A is a semiautomatic scanning approach (Perkin Elmer ABI Pnsm 377 DNA Sequencer) based on chemical cleavage of the mismatch in fluorescently labelled DNA heteroduplexes, obtained from normal and mutated alleles. Pecuhal feature of F A M.A. is the ability to accurately detect and localize mutations For F.A.M A. analysis , 4 fluorescent overlapping PCR amphcons were generated containing respectively the exons 2,3,4 (1074 bp); 5,6,7 (1263 bp); 8,9 (827 bp), 10,11 (1299 bp) P53 gene mutauons of exons 5-9 were actually evaluated

14 pathologic

mutations (26.4 %) confirmed by automatic sequencing analysis and 3 polymorphisms were observed. 9 missensc mutations, 2 mutation at the splice-junction, 3 non-sense mutations Analysis of exons 2,3,4 and 10, 11 is ongoing Among the 14 patients with very high-risk of recurrent disease (vHR, >10 N+), four were p53+ (mutated) Median disease free survival (DFS) was 41 months in p53- (wild-type), 4 months in the 4 p53+ patients In conclusion, accurate detection of p53 mutations in BC patients identify a subset of vHR patients with worse prognosis and potencially resistant to genotoxic drugs.


WEEKLY SCHEDULE OF PACLITAXEL, 5-FU 24 HOURS INFUSION AND FOLINIC ACID A PHASE II STUDY IN METASTATIC BREAST CANCER F.Castiglionc, A.Ventunno, O Ostellino, M Destefams, A.DallaMola, G Porcile Service of Medical Oncology, Civic Hospital, Alba (Italy) E15

Background. Weekly deliveries of pachtaxel have been proven effective and well tolerated in breast, lung and ovarian cancer. Recently also 24 hours infusion of 5-FU has been found effective in breast and colorectal cancer Before our study, no trial had combined these two effective drugs in a weekly schedule for the treatment of metastatic breast cancer. Patients and methods. Based on different toxicity profiles and mechanisms of actions of 5-FU and paclitaxel, with the aim to test regimen effectiveness and compliance of 5-FU 24 hours infusion (expected better than prolonged infusions), we started a phase II study of a weekly schedule of 1 1 1

Paclitaxel, 80 mg/sm over an hour Folinic acid, 500 mg/sm over two hours 5-FU, 2000 mg/sm through 24 hours infusion all given on days 1,8,15.22,29,36

The cycle was repeated after a rest of two weeks, then patients were re-staged and a third cycle (consolidation) was delivered to responding patients. Until now 14 patients were enrolled (median age 57.5 years), all previously treated by antrhracyclincs and seven among them experienced progressive disease in course of treatment or after 6 months) was observed in 71/90 (78.8%) [CR. 3 (3.3%) + PR: 8 (8.8%) + NC> 6 months: 60 (66.6%)] with reduction of the evaluable lesions and symptoms in all the subgroups. Only 9/90 (10%) pts progressed while on therapy. No significant difference was observed among the 3 treatment groups in terms of efficacy and response rate. In conclusion AI have produced a high grade of CB and a low toxicity profile in this subset of pts E14



High-Dose Chemotherapy (HDCT) with Docetaxel(T), Epirubicin (E) and Cyclophosphamide (C) (HD-TEC) for High Risk Breast Cancer patients (HRBC). Clinical Results.

S Cuuen, R Scalamogna, D Vaccan, E Cocorocchio. A Alietn, PF Ferruca, R Paslano, A Di Corato, F Peccaton, C Martinelli. European Institute of Oncology, Mtlano, Italy While the role of HDCT in metastatic breast cancer patients seems to be well defined, it is still under investigation its activity in adjuvant setting Multiple HDCT could demonstrate a possible benefit in HRBC. The HD-EC regimen has been demonstrated to be safe and feasible, and actually clinical results of a prospective randomized trial are under evaluation by International Breast Cancer Study Group (IBCSG) Recent results, suggesting a benefit of adding taxanc to the treatment of localized or metastatic breast cance,could represent a possible improvement in adjuvant setting also principally in HDCT We evaluated toxicity and clinical activity of the addition of T to HD-EC in adjuvant HRBC pts. From June 1998 to March 2000 we enrolled 69 pts with a median age of 43 years (range22-61) All patients underwent surgery, 22 as a part of neoadjuvant therapy, median number of involved axillary nodes was 1 l(rangc 2-49) Most patients were premenopausal and the majority (63%) presented ER+, all pts had to have an adequate bone marrow function and normal liver, renal and cardiotogical function tests Before starting the HDCT program, after the administration of G-CSF (5 Ug/Kg) twice daily for 5 days, at least 6xl06/Kg CD34+ were collected and stored tn 3 fractions Every patients was treated with 3 courses of T (85 mg/sqm) and E (200 mg/sqm) on day 1, and C (4 gr/sqm) on day 2 followed on day 5 by a reinfusion of at least 2xlO'/Kg CD34+ cells All those patients who presented ER+ received Tamoxifen 20 mg/die for 5 years A total of 195 cycles have been evaluated. The median hospitahzation length was 16 days (range 13-29) and the major loxicity observed was mucositis (G2G3) observed in the 55% of the course, during 12% of them we observed a grade 3 mucosius during the 1st cycle No pts required parenteral nulntion or delay on subsequent treatment Cardiac function (EF) was evaluated with echocardiography, and no significant differences in EF rate was observed during and after the end of the enure program With a median follow up of 13 months (range 5-25) and a median DFS of 11(1-20) months only 1 (1.5%) patient died and 4 (6%) pis relapsed. Multiple HDTEC is a safe and feasible regimen, and the addition of T (85 mg/sqm) to HD-EC does not prolong hematological recovery in our experience. The major non-hematological toxicity is oral mucosius. The HD-TEC regimen will be evaluated in a randomized trial of the IBCSG

Final considerations. This weekly schedule of paclitaxel, 5-FU and fohmc acid appears to be safe for prc-treated metastatic breast cancer patients. Dala on response are promising. Moreover 5-FU 24 hours infusion probably saves patient quality of life better than prolonged infusion


Session E: Breast Cancer



T.Coialbu,F.Minervim,M.P.Parodi Divisione Medicina, Day Hospital Oncologico.Ospedale A.Gallino,USL 3 Genovese, Ge-Ponte X, Italia. Breast cancer is the most common tumor in women. Age is a well known risk factor. Older patients affected by breast cancer often suffer comorbidities. Psychological impact has also to be in count in this group of women. Increasing use of breastconserving treatments can partially reduce this negative effect. We reviewed 36 patients older than 70 years admitted to our Institute during the lasl 5 years. The median age was 76 years (r = 70-88). The surgical treatments were: mastectomy for 18 patients, quadrantectomy for 12, lumpectomy for 4, biopsy for 2. Stages according TNM were: 6 T1N0, 3 TINx, 5 T1N+, 8 T2N0, 6 T2N+, 1 T4N0, 4 T4N+, 1 T4Nx, 2 TxNx. Post-surgery treatments were hormonal therapy in 28 cases, adjuvant chemotherapy in 10. In case of conservative surgery 13 patients received radiotherapy while the sole hormonotherapy was reserved for 3 patients with comorbidities, awareness of disease and/or demence An interview about their problems and fears was administered either to all the women able to collaborate or to their relatives. The answers were collected in their record-cards In case of mastectomy patients were found to be distressed because of disease and afraid of future at the beginning of follow-up. On the other hand out of patients who underwent breast-conserving surgery 8 cases were worried about times, modalities and discomfort of radiotherapy in spite of explanations, while 8 cases were satisfied and considered their disease less serious. In the whole group 18 patients (50%) were able to receive precise informations about their disease and possibilities of treatments either while staying in surgery or during the first access at the oncologic day-hospital. A critical factor in the selection of local therapy is patient' s desire and everyone should be given the opportunity of decision-making process. Now efforts are directed to a better collaboration between our surgical and medical departments to decrease the level of distress and increase the good quality of medical facilities also for this group of patients considered more frail.


A PHASE n STUDY OF HUMANIZED ANTI-HER2 MONOCLONAL ANTIBODY (rhuMAB HER2) AND WEEKLY CHEMOTHERAPY IN WOMEN WITH METASTATIC PROGRESSIVE BREAST CANCER Colozza M. (.), Gori S. (.), Mosconi A M (.), Di Stefano A. (*), Mazzoni F. (*), Maestri A. (*), Cherubim R. (.), Cnno L. (*), Tonato M (.) (.) U.O. Oncologia Medica - Policlmico Monteluce - Perugia (*) U.O Oncologia Medica - Ospedale Bellana - Bologna Purpose: Overexpression of the HER protein occurs in 25% - 30% of human breast cancer and is associated with poor prognosis. In this study we evaluated safety and activity of humanized anti-HER2 monoclonal antibody in combination with chemotherapy in a small group of women with metastatic breast cancer progressing after one or more chemotherapy regimens Patients and methods- In 1999 15 women with HER2 - overxpressing metastatic breast cancer in progression after systemic chemotherapy were treated with rhuMAB HER2 and weekly single agent chemotherapy. Patients received a loading dose of 4 mg/kg intravenously followed by a 2 mg/kg maintenance dose at weekly intervals 11 pts received weekly Pachtaxel 70 mg/m2 and 4 pts received Cisplatin 50 mg/m2; 8 pts had been previously treated with 2 and 7 pts with one chemotherapy regimens. Results: All patients had disseminated disease and had received extensive prior chemotherapy. 1 complete remission, 3 partial remissions and 5 stable diseases have been recorded; one patient experienced progression and 5 are too early. In this small experience all responses have been observed with rhuMAB HER2 and Paclitaxel. The median duration of the treatment was 14 weeks (7-47). The most common adverse events were infusionassociated fever and/or chills during the first infusion and were of mild seventy Conclusions: In this small trial humanized anti-HER2 in combination with weekly chemotherapy is well tolerated and active in extensively pretreated women with metastatic breast cancer.

Session E: Breast Cancer


Collina N., Baldazzi P., Capri A., Donato S., Geminiani MX., Panetta A., Portincasa G., Stasi G. Coordinating Unit of the breast cancer screening - Alienda USL Bologna Nord The breast is a leading cancer site in women throghout the world. In Italy around 270.000 new cases are diagnosed each year and 11.000 patients will die from the disease. The overal goal of breast cancer screening is to reduce morbidity and mortality. The assumption is to intervene in the disease process after biological onset but before symptoms develop with the aim of decreasing demolitive surgery and mortality. Mammography has been studied widely and appears to offer the greatest potential for decreasing mortality among the largest group at risk for the disease: women aged 50-69. About 3.000 new cases/year are diagnosed in the Emilia-Romagna Region with 1.000 deaths. In order to decrease mortality, the Region is supporting a mammographic screening program for women 50-69 years old, m all the ASL. Since 24-11-1997 in the district of the Azienda USL Bologna Nord, a two-view mammography has been offered to women aged 50-69, living in its territory. Eligible women are 24.512. Up to 23.559 women were invited to enroll by a letter of invitation, followed by a second in case the first had been left unanswered. The compliance rate was 54.1% for the first examination. Women with positive mammography proved histological cancer in 16.6%, positive fine needle aspiration was confirmed in 93%. The total number of diagnosed cancers was 98: 77 invasive and 21 in situ carcinomas. Among infiltrating breast cancers tumor size was below cm 1 in 48%. Conservative surgery was performed in 77.3% of cases. Our preliminary results are consistent with the regional and national standards and are the basts to carry on an improving but positive program.



E Cortesi, S Rampom, A. Ohva, *F Ferrau, L. Moscetti and F Gnfalchi Medical Oncology Dept Of Experimental Medicine and Pathology, University " La Sapienza ", Rome, Italy * Medical Oncology. S Vincenzo Hospital - Taormina, Italy Introduction Recent studies showed a very good activity and tolerabihty of weekly (w) Paclitaxel (PTX) in pretreated patients with metastatic breast cancer. Protracted conunous infusion (P C I ) 5Fluorouracil (5-FU) has been shown to be very well tolerated and with a marginal activity in this subset of paUents. Objectives- to define the MTD of weekly PTX associated to a fixed dose of 5-FU P C I . (250 mg/m2/day for 3 weeks + 1 week of rest), in metastatic breast cancer patients pretreated with Anthracyclines The starting dose of PTX was 75mg/m2 ,1 hour infusion, (days 1-8-15-22, recycle every 4 weeks) with subsequent dose escalation to 90mg/m2 (II Step) and 105 mg/m2 (III Step). Results. 12 patients were enrolled. Eligibility criteria KPS >70, age>18, adequate bone mairow and renal function, pretreatment with Anthracyclines containing regimens I Step: 7 pts with 1 TDL (C3 Mucosilis) II Step: 3 pts without TDL III Step: 2 pts with 2 TDL (1 G3 Mucositis and 1 Febrile Neutropenia) Side effects- Gl Neurotoxicity (3/12), Gl-2 Dermauus (5/12), Gl-2 Mucositis (4/12), G3 Mucositis (2/12), G2 Diarrhoea (1 /12), Gl Leukopenia (1/12), G2 Neutropenia (3/12), G3-4 Neutropenia (2/12), Gl Anemia (1/12) and Gl Thrombocytopenia(l/i2). Conclusion- The recommended schedule for phase II studies is PTX 90mg/m2 w + 5FU 250mg/m2/day P C I. for 21 days. G3 Mucositis (2pts) and Febrile Neutropenia (1 pi) were the TDL. No Neuroloxicity > Gl was observed A phase II study is ongoing. This study is the first phase I trial with the combination of weekly PTX and 5FU P.C.I, in advanced breast cancer patients.




D'Aiuto G, Frasci G Cornelia P, Thomas R, Capasso I, Botti G, Cortino GR, De Rosa V, and Cornelia G On behalf of the Southern Italy Cooperative Oncology Group c/o National Tumor Institute of Naples Purpose: To define the Cyclophosphamide MTD when combined with fixed doses of Gemcitabine, Fluorouracil and folinic acid in pretreated breast cancer patients Methods. Advanced breast cancer patients (stage IIIB or IV) aged < 70 with ECOG PS 0-2 were eligible provided that they had received a previous anthracychne- and taxane-based chemotherapy for the advanced disease. Chemotherapy consisted of Gem 1,000 mg/m2 + 5FU (425 mg/m2) LFA (100 mg/m2) + escalating doses of CTX (starting from 500 mg/m2) on d 1 & 8 every 3 weeks In the first cohort CTX was given at the dose of 1,000 mg/m2 only on d 1, but the schedule was changed to 500 mg/m2 d 1 & 8 because of the occurrence of severe neutropenia in 3/6 patients..After the definition of the DLT a further escalation with the addition of G-CSF (d 3-5 and 10-12) was planned. Results: Since March 1999, 37 patients entered onto this trial. Level 0 1 2

CTXdose mg/m2 1000* 500 600




6 7 8

28 32 29

3 1 3

type neutrop neutrop. 2 neutrop 1 thrombo neutrop

Response 1 2

3(1 CR) 8 38 1 3 700+ 3 4 2 18 4 800+ 0 4 5 1 too early 900+ 5 neutrop * only on day 1 Conclusions: Our new regimen is well tolerated treatment in poor prognosis breast cancer patients (with previous exposure to both anthracychnes and pachtaxel). With the addition of G-CSF a CTX cumulative dose of 1,600 mg/m2 can be safely delivered every 3 weeks. The evidence of 11 objective responses in the 33 evaluable patients (33%)is very promising The study is still ongoing, but we expect that the final results will be available at the time of the meeting



Background In early breast cancer, several prognostic factors are known while the role of factors in predicting the response to treatment is poorly defined. Methods. The GONO-MIG group conducted a randomized adjuvant-chemotherapy trial (MIG 1) to evaluate the role of dose-dense chemotherapy (CT) in early breast cancer patients (pts) 1214 pts were randomized to receive either CEF21 (cyclophosphamide 600, epirubicm 60, fiuorouracil 600 mg/mq) every 21 d for 6 cycles or the same regimen given every 14 d with the support of G-CSF (CEF14). Tamoxifen (TAM) was given to ER positive pts and postmenopausal pts. Expression of HER2 was retrospectively determined by immunohistochemistry (CB11 MoAb - Biogenex) in 731 patients HER2 status was classified as 0, 1+, 2+, 3+. It was considered negative or weakly positive for values 0, 1+, 2+ or strongly positive for 3+ Statistical analysis were performed to test for interaction between treatment (TAM yes vs no, and CEF14 vs CEF21) and HER2 with respect to overall survival (OS). Results Overexpression of HER2 (HER2 3+) was observed in 103 (14 1 %) of the 731 tumors studied. 108 relapse and 63 deaths were observed Analysis of interaction between HER2 status and treatment showed that treatment with TAM was effective in pts with HER2 negauve tumor (p=.0030), and not in HER2 positive pts (p=.668) On the contrary the potenual benefit of dose-dense epirubicin-containing adjuvant CT is restricted to HER2 3+ pts (see figures below) Overall survival by random Overall survival by random HER-2 negative

HER-2 positive



M De Lena1, P.F Conte2, L. Manzione3, D. Amadori4, L. De! Mastro5, G. Moretti6, F. Gnfalchi7, R. Valsecchi8, S Luzi Fedeli9, R. Lionetto10 and A Gennari2 'Oncology Dept., IRCCS, Bari, 2Oncology Dept S. Chiara Hospital, Pisa, 3Oncology Dept., S. Carlo Hospital, Potenza; "Oncology Dept., Pierantoni Hospital, Forli, 5Oncology Dept., 1ST, Genova, 6Oncology Dept., Spallanzani Hospital, Reggio Emilia; 7Oncology Dept, La Sapienza University, Roma; 8Oncology Dept., S.Carlo Borromeo Hospital, Milano, 'Oncology Dept., S Salvatore Hospital, Pesaro; l0Advanced Biotecnology Center, 1ST, Genova A phase in multicentric randomised clinical trial on rnetastatic breast cancer patients (MBC) is ongoing in order to verify the difference in terms of Progression Free Survival and Overall Survival between maintenance therapy with Paclitaxel (P) (arm A) and no treatment (arm B) after an induction phase with anthracyclines plus taxanes. MBC patients receive one of the following regimens as first line chemotherapy a) Epirubicin 90 mg/sqtn + P 200 mg/sqm (3 hrs) q 21 days, b) Doxorubicm (D) 50 mg/sqm 16 hrs before P 200 mg/sqm (3 hrs) q. 21 days; c) D 50 mg/sqm d. 1 + P 200 mg/sqm d 2 (3 hrs) q. 21 days, for 8 courses Responding and stable patients are randomised to receive further 8 courses of P 175 mg/sqm q 21 or no treatment. To date (30 April 2000), 250 patients have been enrolled in the induction phase and 118 have been randomised: 51.5% in arm A and 48 5% in arm B Main reasons for non randomisation of the enrolled patients are: progressive disease (10%), unacceptable toxicity (4.5%), treatment refusal (6%). Patient characteristics are as follows: median age 55 years (range 30-73), median Performance Status 0 (0-2), 29% of the patients are premenopausal, 58% are ER+, 50% have received prior adjuvant chemotherapy, and 19% hormonal treatment for metastatic disease, 29% of the patients were metastatic ab initio (64% viscera, 21% bone, 15% soft tissue), 37% of patients have 1 metastatic site and 23% have 3 or more metastatic sites. Data on the compliance to maintenance chemotherapy and toxicity will be presented.





Di Costanzo F 1 ; Pronzato P2; Passalacqua R3; De Mattets A4; Cazzaniga M5; Viaggi S6; Fiori G6; Rosso R7 on behalf of the IRIS Study Group. 1) Dipartimento di Oncologia Medica, Azienda Ospedahera Umversitana di Term, Term, Italy 2) Dipartimento di Oncotogia Medica, Ospedale Est Felettino, La Spezia, Italy 3) Divisione di Oncologia, Ospedale Maggiore, Parma, Italy 4) Divisione di Oncologia Medica C, Istituto dei Tumon, Napoli, Italy 5) Unita Operativa di Oncologia, Azienda Ospedaliera Treviglio Caravaggio, Treviglio, Italy 6) Divisione Studi e Ricerche Link Italia, Modena, Italy 7) Istituto Nazionale per la Ricerca sul Cancro, Divisione di Oncologia Medica I, Genova; Italy Introduction: IRIS is a longitudinal multi-center study aimed at investigating the therapeutic modalities employed in post-menopausal women with advanced breast cancer (ABC), in particular the parameters influencing the choice of hormonal versus chemotherapic treatment in ABC Materials and Methods: IRIS is performed in 57 Oncology Centers (OCs), homogeneously distributed throughout the Italian territory. According to the study protocol, each OC is expected to enroll at least 10 women with breast cancer, equally distributed between subjects with new diagnosis of ABC (PM. Prospective Metastases) and pts widi diagnosis of ABC within 1 yr before entering in this trial and no more than 2 treatments performed for progression of disease (RM Retrospective Metastases). Follow-up is performed every 3 months or when there is evidence of disease progression Results: a number of 463 women was enrolled on this study from June 1999 to 18 April 2000. PM and RM subjects were 565 and 43.5%, respectively. Median age was 61 2 yrs. Metastases were most frequently found in bones (56%), lungs (28%) and liver (23%). Fifty-one percent of women had undergone hormonal therapy for metastases Other therapies for metastases were performed in the following percentages, chemo 69%, RT 70%, and surgery 8% The 23% of the patients had undergone both hormonal therapy and chemo. The choice of hormonal treatment was influenced mainly by adherence to international guidelines (39%), localization of metastases (31%), biological charactensucs of the tumor (29%), age (23%), disease-free interval (16%), performance status (12%) and patient's compliance (12%) About 30% of the enrolled patients have already attended at least 2 F-UP visits Conclusions: IRIS is expected to improve our understanding of the factors involved in the choice of treatment in women with ABC outside the clinical trials

Conclusion. This analysis suggests a potential role of HER2 as indicator able to select patients who may benefit from dose-dense epirubicin-containing adjuvant CT Furthermore, our data confirm a lack of benefit from adjuvant Tamoxifen in patients with tumor overexpressing HER2.


Session E: Breast Cancer




L. Di Cristina*, D. C i m t o , " S. Vitello*"


*Servizio di Oncologia, Alcamo (TP); **Repano di Chirurgia, Ospedalc S. Elia; ***Servizio dj Oncologia, Ospedale S Eha di Caltanissetta

Angelo Dinota, Antonio Rossi, Domenico Bilancia, Gerardo Rosati, Luigi Manzione Medical Oncology Unit, "San Carlo" Hospital, Potenza - Italy

Salvatage treatments in metastatic and pretreated breast cancer are, in general, of little effect and of short duration (R.O. 10-15% and 5 days, G 3-4 PTL, any persistent > G2 side-effect causing delay of 1 wk in 2/3 pts at a single dose level since delay of recycling could results in a significant reduction in planned dose-intensity (PDI). Results of the phase I study may be summarized as follows : step 1, 3 pts DCT 40 mg/m2 (d 1,16 ) no G4 tox, no reduction in PDI in all pts; step 2, 3 pts DCT 50 mg/m2 (d 1,16) no G4 tox, no reduction in PDI in all pts, step 3, 3 pts DCT 60 mg/m2 (d 1,16) G3 neutropenia, reduction of DI in 1/3 pts, fatigue in 1/3 pts (MTD); step 4, 3 pts DCT 70 mg/m2 (d 1,16) persistent neutropenia which caused reduction of PDI in 2/3 pts, fatigue in 2/3 pts (DTL). PDL delivered DI, and G3-4 tox were : 25 mg/m2/wk, 21 9 mg/m2/wk, neutropenia 48% pts, fatigue G2-3 DCT 75 mg/m2 q 3 wks, while 25g/m2/wk, 23.6 mg/m2/wk, and no neutropenia G4, fatigue Gl for DCT 50 mg/m2 q 16 days ORR was 44% for 16 pts treated with DCT 75 mg/m2/3 wks, and 47% for 32 pts with DCT 50 mg/m2 q 16 days. Bi-monthly administration of DCT is feasible and allows full dose drug delivery while reducing toxicity with a slight increase of frequency of administration. Both weekly and bi-monthly schedule may allow the use of DCT in combination with other drugs without improving toxicity.


NEOADJUVANT CHEMOTHERAPY IN OPERABLE BREAST CANCER Giardina G, Chini C; Fagnoni E;Pigm A; Membnni F, Rodolfo Masera L, Proserpio I; Martinelli B and Pinotti G Oncologta Medica — Azienda Ospedaliera di Circolo e Fondaztone Macchi, Varese, Italy Neoadjuvant chemotherapy is emerging as a new approach for treatment of breast cancer (BC). The benefits of primary systemic therapy include the downstaging of the tumor, facilitating surgical removal, increasing breast conservation rates and front-line treatment of micro metastatic disease, possibly ameliorating the outcome of patients (pts) Studies in the last few years indicate a clinical response rates of 30-90% with clinical reported complete remission (cCR) of 10-35% and pathological complete remission (pCR) of 10-20%. The aim of this study is to evaluate the efficacy of different primary chemotherapy regimens in 38 women with previously untreated BC referred to our centre over a 3-year penod Patients characteristics: median age: 52.5 years (range 32-71), stage at presentation Twb, No-i; median tumor size: 3.9 cm (range 2.5-10). Treatment: Epirubicin alone (120mg/mq every 21 days) in 18 pts; ECF regimen in 11 pts; PEV regimen in 4 pts; FEC regimen in 1 pt; EC regimen in 3 pts and CMF regimen in 1 pt. Response was assessed by standard criteria; pCR was assigned only if no neoplstic cells were detected by pathologists in the breast tissue specimen and axillary nodes removed at surgery With a median of 3 6 cycles (range 2-6), 6 pts (15.4%) achieved cCR and 24 pts (63.6%) a partial remission (PR); stable disease (SD) was observed in 7 pts (18.4%) while 1 pts (2.6%) progressed during the treatment. Median tumor size, evaluated after 2 cycles and at the end of chemotherapy, was 2.3 cm (range 0.6-6) and 2.1 cm (range 0-6) respectively. Four of 6 pts (10.5%) in cCR presented a pCR and 2/6 pts (5.2%) were found to have only microscopic residual breast tumor. In the population studied, ECF regimen seemed to be the most effective in term of tumor downstaging and pCR; ECF produced a tumor size reduction > 75% while epirubicin downstaging was < 50%, all except one pCR and 2 microscopic residual disease occurred with ECF. It is interesting to note that, surprisingly, in the series of pts treated with ECF the degree of local response does not correlate with size or type of tumor, nodal status, ER/PR setting and predictive factors (Ki67, p53 cerbB2), probably indicating that the mam determinant of survival is the presence of micrometastasis rather than the degree of local control. It would be advantageous however to follow this group for a longer period to see if this favourable response is beneficial in term of disease-free and overall survival Further studies, involving a larger number of pts, are warranted to focus the most effective neoadjuvant chemotherapy regimen, treatment duration and prognostic factors in order to optimise disease control.




Vita Leonard]. Roberto Valenza, Agata Laudam, Catenna Calabria, Giacomo Rondello e Biagio Agostara Medical Oncology Division, Oncologic Hospital "M. Ascoh" , Palermo

Refractory metastatic breast cancer is one of the most controversial area for medical oncologists. No salvage treatment to date is believed to modify patients clinical outcome and even if objective response are seen, most patients do not receive a real benefit, in term of survival, from their chemotherapy. Nonetheless, women with a good performance status, almost complete absence of symptoms usually expressly request therapy continuation. In this study 22 pretreated advanced breast cancer patients were enrolled and treated with Carboplatin AUC 5 i v d 1 and VP16 100 mg/m2 i.v. d 1-3, every 28 days. The main patients's characteristics were: mean age 53.4 years, PS (ECOG) 0-2, the sites of disease were as follow, liver 54 5%, lung and bone 50%, skin 36.3%, nodes 31.8%, pleura and brain 27.2%, breast 9%, other 13.5% The 72.7% of enrolled patients had more than 3 sites of disease. Previous treatment consisted of surgery for 100%, radiotherapy for 31.7% and ormonotherapy for 77.2% of patients; the 86.3% had received previous adjuvant chemotherapy, all patients but five (77.2%) had received previous treatment with antracycline and/or taxane containing chemotherapy for advanced disease. 14 patients (63.6%) had received more than two regimen, 9 patients (40.9%) had received also a third chemofherapeutic treatment. A total of 67 cycles were delivered with a mean of 3 cycles per patients (range 1 - 7). Out of 13 evaluable patients (9 patients too early) we obtained 3 partial remission (23%) with a mean duration of 7.3+ months (4+ - 10+) and 5 stable disease (38.4%) with a mean duration of 6.6+ months, whereas 5 patients (38.4%) had progressive disease. The mean overall survival was 8.6+ months Out 20 evaluable patients (2 patients too early), the main toxicity registered was gastrointestinal (55%) with N/V G2 in 6 patients (30%); the hematological toxicity was moderate with neutropenia G3-4 in 15% of patients and thrombocytopenia G3 in 1 patient (5%). Other side effects were negligible. In conclusion the small number of enrolled and evaluable patients does not permit to make any conclusion. Is necessary to continue the study and to enlarge the casuistry




Lauro S., Izzo P.*, Trasatti L., Bria E., Gelibter A., Larosa G., Reale M.G., Vecchione A,, Frati L Department of Experimental Medicine and Pathology, University of Rome "La Sapienza", *2^ University ofRome"Tor Vergata", ITALY. PURPOSE- In order to define the clinical uulity of serum markers as indicator of therapy effectiveness in advanced breast cancer, levels of CEA, CA 549, TPS and CA 15-3 were analyzed in 48 patients (median age 52 years, with range 32-78 years). METHODS. Markers were determined before, during and after therapy (chemotherapy and/or hormonotherapy) and the serial values were compared to clinical response to treatment. Five ng/ml for CEA, 30 U/ml for CA 15-3, 10 U/ml for CA 549 and 80 U/l for TPS were considered as upper reference levels. Disease progression or response to therapy were determined by instrumental techniques (chest-X-ray, bone scan, liver ultrasonography). RESULTS We observed a better correlation with clinical course of disease for CA 15-3 and TPS compared to the others checked markers: CEA was correlated to clinical response in rale of 45%, CA 549 in 63%, CA 15-3 in 70% and TPS in 68%, its levels decreased significantly also in stable disease The combined use of complete markers panel increased sensitivity concerning treatment response not substantially (73% vs 70%). CONCLUSION Although CA 15-3 and CEA are the most commonly used tumor markers during the last ten years, we believe that a new approach is to combine CA 15-3 with TPS during therapy and that their serial determinations can be useful, easy, complementary tools for predicting clinical response.


DOCETAXEL EVALUATION OF Trffi ACTIVITY AND TOXICITY IN SECOND LINE OF METASTATIC BREAST CANCER (MBC) PATIENTS (PTS) V Liguori, A Filice, R. Biamonte, S. Conforti, CM Mastroianni, A. Rovito, R. De Simone, C. Manfredi and S. Palazzo Department of Oncology - Mariano Santo- Cosenza- Italy Docetaxel has proved to be active in pts with metastatic breast cancer, where the treatment with single or combination chemotherapy is generally disappointing. Between 6-1998 and 12-1999, Docetaxel (100 mg/mq lh i.v.) with Desametasone pre and post medication and Ondansetron 8 mg i.v., was administered to 25 pts with MBC, every 3 weeks. The toxicity was evaluated with Quality-life (QOL) Questionnaires too PATIENTS DATA • median age 58 years, PS 0-1(18 pts) 2 (7 pts). Previous adjuvant chemoterapy anthracychnes (8 pts) CMF (9 pts). Previous palliative- anthracychnes (19 pts), HD+PBSC (2 pts), Taxolo (2 pts) .Vinorelbine (2 pts). Dominant metastatic side, soft tissue 8 (32%) bone 9 (36%) lung 9 (36%) liver 7(28%); number of metastatic side: 1(15 pts), 2(7 pts), 3(3 pts). TOXICITY: 3 pts stopped treatment for WHO G4: 1 asthenia and 2 dyspnea. Nausea/vomiting (Gl)60% ,(G2)32%;stomatitis/ulceration(Gl)4%;alopecia 100%;hematological(G 1 )36%,(G2)8% ;asthenia(G I )40%,(G2)28%,neuropathy(G 1)20%, (G2)4%; skin rash(Gl)8% The mean number of cycles administered was five(l-l 1). RESULTS :response was evaluated in 21 pts The overall response rate was 28.5%(4 76%complete response).The response rate was 66.6% soft tissue, 14 2% bone,40% lung 20% liver The median response duration was 4 months(2-16+) Comparing baseline QOL parameters pts responding maximum overall health, after 3 cycles, despite an improvement in pain, indicated a worsening of overall health in terms of emotional and social functions(65-5% reduced to 36%). CONCLUSION: Docetaxel is active in pts with heavily pretreated breast cancer,but response duration is some months, so drug toxicity for quality of life become extremely important.

Session E: Breast Cancer



Maiorino L, G, Frasci G, D'Aiuto G, Cornelia P, Carteni G, Thomas R, Capasso I, Cortino GR, DeCataldis G, Silvestro L, Russo A., Di Bonito M, and Cornelia G. on behalf of the Southern Italy Cooperative Oncology Group (S1COG) do National Tumor Institute Naples - ITALY

Background: In a previous phase n study the PET weekly regimen gave an ORR of about 80% in breast cancer patients with metastatic disease, while the ORR exceeded 90% in those with locally advanced disease (Frasci G et al: Breast Cancer Res and Treat in press) Patients and methods. Patients (pts) with locally advanced (T4 or N3) or metastatic disease, ECOG P S 0-2, age < 70 years, and measurable disease are eligible Women are randomized to receive: PET: P 30 mg/m2 + E 50 mg/m2 + T 120 mg/m2 weekly for a maximum of 12 cycles (G-CSF is also given each week d 3-5) or ET- E 90 mg/m2 + T 175 mg/m2 q3wk for a maximum of 6 cycles Study design:Time to treatment failure (TTF) is the end point for the statistical inference. Hypothesizing in the chosen study population a 9-month median TTF for ET, we aim at evaluating whether a 3-month prolongation of this parameter can be achieved with PET. Setting alpha= 0.05 and l-beta= 80%, at least 130 patients are required in each arm. An interim analysis has been planned after half of the total number of patients has been enrolled. Results: As of May 12"', 2000, 87 women have entered onto the trial (PET=44, ET=43) 42 pts. have locally advanced and 45 metastatic disease 16/45 of the latter have received previous adjuvant chemotherapy Visceral involvement is present in 26/45 pts. with distant metastases. Overall, 278 weekly PET cycles and 134 ET tnweekly cycles have been delivered. No treatment-related deaths have been observed. Grade 4 neutropenia and thrombocytopenia have occurred as follows: PET: N=12%, T=2%; ET N=49%, T=15%. Grade 3-4 nonhematologic toxicity has been substantially more frequent in PET arm (27% vs. 14%) Conclusions: Both PET and ET regimen represent a well tolerated therapeutic approach for breast cancer patients with advanced disease The accrual still conti nues and we expect that the results of the planned interim analysis will be available at the time of the meeting.




S. Masserom*; D. Tabiadon*, L. Frontini+; R. Labianca 0 ; G. Schieppati A ; N. Tosca"; R. Biasioli'; G. Luporini* *San Carlo Borromeo H Milan; +San Paolo H. Milan; °H. Riuniti Bergamo; Saronno H. Saronno; Sacco H. Milan; Magenta H Magenta The treatment of MBC tn elderly pts very often represents a problem because of their compromised general conditions .other concomitant diseases and low compliance. Oral administration of drug with proven efficacy and acceptable toxicity could be an interesting therapeutic opportunity. SFIuorouracil (5FU) is a widely used drug in the treatment of metastatic breast cancer. Phase II study results demonstrate good efficacy and low toxicity following continuous infusion of low dose 5FU in heavily pretreated pts with MBC. Citofur allows a prolonged exposure to 5FU without the need for central venous catheters or infusion pumps. Several phase Et studies with oral Idarubicin in elderly naive antracycline breast cancer pts demonstrated an acceptable efficacy with a low toxicity. On this basis, since March 1999 we started a multicentre phase II study with oral Idarubicin and Cuofur as first line chemotherapy in elderly MBC pts. Till March 2000 we treated 18 pts older than 70 years, 16 were evaluable for toxicity and response. 25 mg p.o on day \°-8o-\5° every 28 days ScheduleIdarubicin cp Citofur cp 400 mg p.o from dayl to day 14 every 28 days Folinc Acid 30 mg p.o from dayl to dayl4 every 28 days Patients Characteristics All the pts were older than 70 with MBC at first presentation with adequate cardiac, hematopoietic, kidney and liver functions. Median age was 76 (range 7088); 9 pts had soft tissue metastasis, 8 bone and 14 had visceral metastasis. 5 pts had only 1 site of disease, 12 pts had 2 sites and 1 had 3 sites of metastasis. Reiulu.:68 courses of therapy were completed RO= 25% (RC=2 pts; RP=2 pts;) R0+RM+SD= 50% (RM= lpts; SD=3pts) Main toxicity: No grade 3-4 toxicity was observed except alopecia in 1 pt; grade 2 toxicity were nausea and vomiting in 2 pts and anemia in 1 pt. Conclusions: An interim analysis made on March 2000 demonstrated an acceptable rate of response, in agreement with literature in this subset of pts, but an absolute absence of relevant toxicity. On this basis we decided to increase the dose of oral Idarubicin in order to achieve a better response rate keeping low toxicity.

Session E: Breast Cancer



(pts) WITH VINORELBINE (V) AND SFU IN PROTRACTED I.V. INFUSION (p.i.). A PHASE I TRIAL. A.Malossi", R.MarUnotu°, I.Chiappino", M A.SatoIli", M.Mistrangelo°, M.Tetti", F Angelim", OAlabiso* °U O.D.U Chir. Oncologica, Dir. Prof. A.Mussa, A.O. S Giovanni Battista, Torino. *Univ. degli Studi del Piemonte Onentale "A.Avogadro", Novara Aim: evaluate toxicity and efficacy of SFU and Vinorelbine containing schedule in pts with metaslauc breast cancer pre-trcated with Taxanes and Anthracychnes as either adjuvant or pallative therapy. Methods' In phase I study 10 pts were treated with V administered as bolus i.v. infusion on day 1,5 q21 and 5FU as protracted infusion, desamethasone 4 mg was administered during V infusion in order to avoid flebitis. Dose levels used to define the MII) are showed in table. Vinorelbine SFU mg/m'/die Cohortes Patients mg/m 1 200 6 25 4 2 250 25 The MTD was reached at V 25 mg/m2 and 5FU 250 mg/m'/die So we are treating pis for phase II study with drugs dosage used in first cohort. Results From September 1998 up to now 17 pts enrolled (10 phase I, 7 phase II)- M/F: 1/16, mean age 59y, PF ECOG 2 3%) were randomized to receive arm a) 6 cycles of adjuvant polichemotherapy according to FEC scheme, arm b) no therapy until disease progression. 125 and 123 patients treated with radical surgery for pTl-2N0M0 breast cancer were randomized in FEC and Control Arms, respectively After 70 mo. of median follow-up, 27 (21.6%) and 39 (32 2%) events were observed in FEC and Control arms, respectively with a significant lower number of locoregional relapses in FEC group. A 5 yrs DFS of 81 % in FEC arm's women with respect to 69% of the Control group was observed (p 2 years < 5 years, median age 49 years (range 30-70); P.S ECOG (0): 10 pts ; (1) :6 pts ; (2) :1; 8 were premenopausal and 9 postmenopausal patients. TREATMENT SCHEDULE : PreMenopause Day 1' Goserelin 3 6 mg s c. (every 28 days) Pamidronate 90 mg I.V. (every 21days) Day 2 Docetaxel 100 mg/m2 i.v. (every 21 days) Day 24 Letrozole 2.5 mg/die p o. (until progression disease or > 1 year) r


Postmenopause: Day 1: Pamidronate 90 mg i.v. (every 2Idays) Docetaxel 100 mg/m3 i.v. (every 21 days) Day 23 Letrozole 2.5 mg/die p.o. (until progression disease or > 1 year) RT treatment started 3 weeks after the last docetaxel course (6Ih), in both arms.




Ucci, G , Vismi, M , Valenum, D., Aondio, G.M., Ferrando, P. -1° Divisione di Medicina Interaa cd Oncologia Medica, Ospedale "Alessandro Manzom" Lecco. ViFUP (vinorelbine 20 mg I V. on day 1 and 3, Cisplatin 60 mg/mq day 1, CI 5-FU 200 mg/mq; repeat every 21 days) is an effective and well tolerated regimen for first line chemotherapy of MBC (Proc.ASCO 1999 113a) We emploied this regimen also in pretreated MBC and report herein data concerning its effectiveness and toxicity From 1.12.1998, 12 MBC patients (one man and 11 women; age 51-73yrs) with multiple metastauc sites (liver 7 pts, lung 7 pts, bone 3 pts, nodes 5 pts, skin 1 pt) were treated. Treatment was planned for 3 cycles responsive patients conunued for further 3-5 cycles and then remained on 5FU C I. for 6 more months. Three patients had received no prior chemotherapy for MBC (all received adjuvant anthracyclines; one relapsed while on adjuvant therapy) ancW pts had been previously treated with one (7 pts) or two (2 pts) lines of chemotherapy Among pretreated patients, 6 had received both taxanes and anthracyclines (either alone or in combination) and 3 had received at least one of these drugs; 5 pts had responded at least to one line while 4 pts were non responders Of the 7 patients who had completed at least 3 cycles of ViFUP, 6 had a partial response while one had progressive disease Among responsive patients, one had not responded to previous anthracyclines and taxanes, 4 had responded at least to one of these drugs and 1 had not received prior therapy for MBC. All responding patients are sail on response 4-16 months after starting treatment, three have completed at least 6-8 cycles of ViFUP and presently are on 5FU C.I. Toxicity was evaluated in 55 cycles and was mild: one episode of superficial flebitis following infusion of vinorelbine, two pts experienced mild hand foot syndrome while mild mucositis and G2 leukopenia led to treatment delay in one case. Notably, alopecia was substantially absent or mild We conclude that ViFUP is an effective and well tolerated regimen even in pretreated patients with MBC, further patients are being evaluated for treatment.

TOXICITY haematologic grade I1I-IV was not registred .while nausea/emesis grade I-II was described in 14 % of courses, asthenia, and myalgias grade I/IT in 10 % of course and alopecia grade HI in 12/17 pts. RESULTS : 14/17 pts with 14/14 OR after only three courses of treatment were registred (4CR+ 10 PR) CONCLUSIONS . Preliminary data observed are very interesting 4 CR after only three cycles , optimal tollerance high and rapid efficacy. The study is still ongoing and forecasts a 40 pts total accrual in the next year.


GEMCITABINE PLUS EPIRUBICIN PLUS TAXOL (GET) IN METASTATIC BREAST CANCER (MBC) PATIENTS (PTS)- A MULTICENTRIC PHASE II STUDY. SDonati*. A Gennari*, P F Conte*, G.L Cetto°, A Molino0, L. Cnno'§, FMazzom§, E Galligioni* M. Mansutti0. *Dipartimento di Oncologia Medica Ospedale S. Chiara Pisa, "Divisione Clinicizzata Oncologia Medica Ospedale Civile Maggiore Verona, §U O Oncologia Ospedale Bellaria Bologna, A Divisione Radiologia e Oncologia Ospedale S Chiara Trento, "U.O. Oncologia Ospedale S Maria della Misericordia Udine A phase II study was performed to evaluate the feasibility and activity of GET regimen in MBC pts. Treatment consisted of G 1000 mg/sqm days 1 and 4 plus E 90 mg/sqm day 1 plus T 175 mg/sqm day 1 every 21 days up to 8 cycles Thirty-six pts entered the study The regimen showed a good tolerability and a high response rate with an overall response rate of 92% and a complete response rate of 31 % At a median follow up of 20 months (10-32), median PFS is 21 months and 30/36 pts are alive. To confirm the feasibility of the GET regimen a multicentric study has been started in 7 Italian centers. Up to now 39 pts have been enrolled. Median age is 52 years (37-68), median PS is 0 (0-1). Hormonal receptor status is: positive in 65% of the pts, negauve in 28% of the pts and unknown in 7% of the patients. Sixty-nine % of the patients received prior adjuvant chemotherapy (17% containing anthracyclines). Dominant metastatic sites arc viscera in 86% of the pts and soft tissue in 14% Number of metastatic sites is- 1 in 21%, 2 in 52% and > 3 in 2% of the pts, respectively Grade 3/4 neutropenia occurred in 59% of the cycles with 4 episodes of febrile neutropema, while grade 3-4 anemia and thrombocytopema were mild (2% and 7% of the cycles) Main non hematological toxicitics were mucositis (G3 in 5% and G4 in 3% of the cycles, respectively), cutaneous toxicity in (G2 in 20% of the cycles). Grade 1 peripheral neuropathy was observed in 13% of the cycles Up to now, only 9 pts have received > 6 cycles of GET. Preliminary evaluauon of activity shows an overall response rate of 58% with a CRR of 10%. If the trial will confirm the tolerability and the high level of acuvity of this regimen, the combination will be tested in raridomized trials




E Landucci, B Salvador], S Donati, M. Rondini, C Orlandim.A. German, P.F Conte Division of Medical Oncology, Santa Chiara Hospital, Pisa. The aim of the present study was to evaluate the ORR, PFS and OS of patients who received GET or ET for metastatic breast cancer after an adjuvant anthracycline containing therapy. From 1995 to 1999 130 patients received an Epirubicin / Pachtaxel combination as first line chemotherapy for metastatic breast cancer in our institution. Of these 27 had been treated with an antracycline containing regimen ( 3 FAC; 1 ABELOFF, 23 FEC) in the adjuvant setting., median RFS was 26.5 months ( range 6-! 11). None of these patients showed primary resistance to anthracycline Median age was 52 years ( range 25-72); median PS 0 ( range 0-2), 34% of the pauenls were ER + , metastauc sites were viscera 64%, bone 30% and soft tissues 6%, 28% of the patients had one involved metastauc site, 26% two and 46% < three. The ORR in these 27 pauenls was 85%, the PFS was 12 6 months and the OS was 24.7 months Among patients who didn't receive an anthracycline in the adjuvant setting (103) we observed an 84% ORR, with PFS of 15 months and an OS of 27 months An Epirubicin / Taxol containing regimen as first line for metastauc breast cancer is acuve even in pauents who received an anthracycline adjuvant setting Moreover the lower cardiotoxicity of Epirubicin allows the safe administration even in patients who received an anthracycline based adjuvant regimen up a cumulative dose of 990 mg of Epirubicin is reached.

Session E: Breast Cancer