MEDICAL POLICY POLICY TITLE

HIGH-DOSE CHEMOTHERAPY AND HEMATOPOIETIC STEM CELL SUPPORT FOR EPITHELIAL OVARIAN CANCER

POLICY NUMBER

MP-9.017

Original Issue Date (Created):

August 23, 2002

Most Recent Review Date (Revised):

September 9, 2008

Effective Date:

July 1, 2009- RETIRED

I.

DESCRIPTION/BACKGROUND High dose chemotherapy (HDC) involves the administration of cytotoxic agents using doses several times greater than the standard therapeutic dose. The most significant side effect is marrow ablation. Therefore, HDC is accompanied by a reinfusion of stem cells to repopulate the bone marrow. There are two sources of autologous stem cells as follows: Autologous bone marrow cells: Bone marrow cells, including stem cells, can be harvested from the patient’s own bone marrow prior to the cytotoxic therapy. Peripheral autologous stem cells: Small numbers of stem cells circulate in the peripheral blood and can be harvested via a pheresis procedure. A prior course of chemotherapy (typically cyclophosphamide) or growth factors, or both, can increase the number of circulating stem cells. Peripheral stem cells are now the most common source of stem cells used. Epithelial ovarian cancer is one of the most common causes of cancer in women and accounts for four percent (4%) of all cancers in women. In this policy the term “ovarian cancer” will refer exclusively to epithelial ovarian cancer. All stages of ovarian cancer are first treated with cytoreductive surgery, including bilateral salpingooophorectomy and total abdominal hysterectomy. While this may be sufficient treatment for cases confined to the ovary, typically intraperitoneal spread is identified; therefore, surgery is commonly followed by chemotherapy. Paclitaxel/platinum combinations are the standard first-line chemotherapy. However, the frequent recurrence of ovarian cancer has prompted interest in high dose chemotherapy and autologous stem cell support. A variety of patient groups have been studied as follows: 

As initial treatment



Treatment of relapse after an initial favorable response to platinum-based chemotherapy



Treatment of tumors whose initial response lasted less than six (6) months



Treatment of refractory tumors.

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MEDICAL POLICY POLICY TITLE

HIGH-DOSE CHEMOTHERAPY AND HEMATOPOIETIC STEM CELL SUPPORT FOR EPITHELIAL OVARIAN CANCER

POLICY NUMBER

MP-9.017

II.

DEFINITIONS ALLOGENEIC refers to having a different genetic constitution but belonging to the same species, i.e., involves a donor and a recipient. AUTOLOGOUS refers to originating within an individual, i.e., self-donation. CYTOREDUCTIVE refers to cellular killing, usually of cancerous clones, with chemotherapy. CYTOTOXIC AGENT is any pharmacologic compound that inhibits the proliferation of cells within the body. INTRAPERITONEAL refers to within the peritoneal cavity. PHERESIS refers to the removal of blood or other body fluids from a patient, separating certain elements (e.g., immunogloblulins, platelets, or red blood cells) and reinfusing the remaining elements into the patient. SALPINGOOOPHERECTOMY refers to excision of an ovary and a fallopian tube.

III.

POLICY High dose chemotherapy with autologous or allogeneic stem cell support is considered investigational as a treatment of epithelial ovarian cancer, as there is insufficient evidence to support a conclusion concerning the health outcomes or benefits associated with this procedure. Cross-references MP-2.201 CA-125 MP-9.021 High Dose Chemotherapy and Hematopoietic Stem Cell Support as a Treatment of Germ Cell Tumors

IV.

EXCLUSIONS N/A

V.

BENEFIT VARIATIONS The existence of this medical policy does not mean that this service is a covered benefit under the member's contract. Benefit determinations should be based in all cases on the applicable contract language. Medical policies do not constitute a description of benefits. A member’s individual or group customer benefits govern which services are covered, which are excluded, and which are subject to benefit limits and which require Page 2 [Note: Final page is signature page and is kept on file, but not issued with Policy.]

MEDICAL POLICY POLICY TITLE

HIGH-DOSE CHEMOTHERAPY AND HEMATOPOIETIC STEM CELL SUPPORT FOR EPITHELIAL OVARIAN CANCER

POLICY NUMBER

MP-9.017

preauthorization. Members and providers should consult the member’s benefit information or contact Capital for benefit information. VI.

DISCLAIMER Capital’s medical policies are developed to assist in administering a member’s benefits, do not constitute medical advice and are subject to change. Treating providers are solely responsible for medical advice and treatment of members. Members should discuss any medical policy related to their coverage or condition with their provider and consult their benefit information to determine if the service is covered. If there is a discrepancy between this medical policy and a member’s benefit information, the benefit information will govern. Capital considers the information contained in this medical policy to be proprietary and it may only be disseminated as permitted by law.

VII. REFERENCES BCBSA 1998 TEC Assessments; Tab 6. BCBSA 1999 TEC Assessments; Tab 11. Bertucci F, Viens P, Delpero JR et al. High-dose melphalan-based chemotherapy and autologous stem cell transplantation after second look laparotomy in patients with chemosensitive advanced ovarian carcinoma: long-term results. Bone Marrow Transplant 2000; 26(1): 61-7. Bertucci F, Viens P, Gravis G, et al. High-dose chemotherapy with hematopoietic stem cell support in patients with advanced epithelial ovarian cancer: analysis of 67 patients treated in a single institution. Anticancer Res 1999; 19(2B): 1455-61. Centers for Medicare and Medicaid Services (CMS) National Coverage Determination (NCD) 110.8.1, Stem Cell Transplantation. Effective 11/28/05. CMS [Website]: http://www.cms.hhs.gov/mcd/viewncd.asp?ncd_id=110.8.1&ncd_version=4&basket=n cd%3A110%2E8%2E1%3A4%3AStem+Cell+Transplantation. Accessed June 4, 2008. Cook S, Penson R, Duska L, et al. Efficacy and hematologic toxicity of salvage chemotherapy following stem cell-supported high-dose chemotherapy in women with recurrent ovarian cancer. Gynecol Oncol 2000; 77(1): 48-54. Cure H, Battista C, Guastalla JP, et al. Phase III randomized trial of high-dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) support as consolidation in patients (pts) with advanced ovarian cancer (AOC): 5-year follow-up of a GINECO/FNCLCC/SFGM-TC study. Abstract No: 5006. American Society for Clinical Oncology. 40th annual meeting. New Orleans, Louisiana. June 5-8, 2004. Donato ML, Herschensohn DM, Wharton JT, et al. High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of advanced ovarian cancer. Gynecol Oncol 2001; 82(3): 420-6.

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MEDICAL POLICY POLICY TITLE

HIGH-DOSE CHEMOTHERAPY AND HEMATOPOIETIC STEM CELL SUPPORT FOR EPITHELIAL OVARIAN CANCER

POLICY NUMBER

MP-9.017

Donato ML, Aleman A, Champlin RE, et al. Analysis of 96 patients with advanced ovarian carcinoma treated with high-dose chemotherapy and autologous stem cell transplantation. Bone Marrow Transplant 2004; 33(12): 1219-24. ECRI Windows on Technology. High-dose Chemotherapy with Autologous Bone Marrow or Peripheral Stem Cell Transplant for Epithelial Ovarian Cancer. 12/2004. Ledermann JA, Herd R, Maraninchi D, et al. High-dose chemotherapy for ovarian carcinoma: long-term results from the Solid Tumour Registry of the European Group for Blood and Marrow Transplantation (EBMT). Ann Oncol 2001; 12(5): 693-9. Mosby's Medical, Nursing, & Allied Health Dictionary, 6th edition. Morgan RJ, Doroshow JH, Leong L et al. Phase II trial of high-dose intravenous doxorubicin, etoposide, and cyclophosphamide with autologous stem cell support in patients with residual or responding recurrent ovarian cancer. Bone Marrow Transplant 2001; 28(9): 859-63. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Ovarian Cancer. Version 1.2008. [Website]: http://www.nccn.org/professionals/physician_gls/PDF/ovarian.pdf. Accessed June 4, 2008.Peethambaram PP, Long HJ. Second-line and subsequent therapy for ovarian carcinoma. Curr Oncol Rep 2002; 4(2):159-64. Prince HM, Rischin D, Quinn, M, et al. Repetitive high-dose topotecan, carboplatin, and paclitaxel with peripheral blood progenitor cell support in previously untreated ovarian cancer: results of a Phase I study. Gynecol Oncol 2001; 81(2): 216-24. Pujade-Lauraine E, Cure H, Battista C, et al. High dose chemotherapy in ovarian cancer. Int J Gynecol Cancer 2001; 11(Suppl 1): 64-67. Rosti G, Ferrante P, Ledermann J, et al. High-dose chemotherapy for solid tumors: results of the Shinozuka T, Miyamoto T, Muramatsu T, et al. High dose chemotherapy with autologous stemcell support in the treatment of patients with ovarian carcinoma: long term results for 105 patients. Cancer 1999; 85(7): 1555-64.e EBMT. Crit Rev Oncol Hematol 2002; 41(2): 129-40. Sarosy GA, Reed E. Autologous stem-cell transplantation in ovarian cancer: is more better? Ann Intern Med 2000; 133(7): 555-6. Shinozuka T, Miyamoto T, Muramatsu T, et al. High dose chemotherapy with autologous stem cell support in the treatment of patients with ovarian carcinoma: long term results for 105 patients. Cancer 1999; 85(7): 1555-64. Stiff PJ, Veum-Stone J, Lazarus HM, et al. High-dose chemotherapy and autologous stemcell transplantation for ovarian cancer: an autologous blood and marrow transplant registry report. Ann Intern Med 2000; 133(7): 504-15. Stiff PJ, Shpall EJ, Liu PY, et al. Randomized Phase II trial of two high-dose chemotherapy regimens with stem cell transplantation for the treatment of advanced ovarian cancer Page 4 [Note: Final page is signature page and is kept on file, but not issued with Policy.]

MEDICAL POLICY POLICY TITLE

HIGH-DOSE CHEMOTHERAPY AND HEMATOPOIETIC STEM CELL SUPPORT FOR EPITHELIAL OVARIAN CANCER

POLICY NUMBER

MP-9.017

in first remission or chemosensitive relapse: a Southwest Oncology Group study. Gynecol Oncol 2004; 94(1): 98-106. Taber's Cyclopedic Medical Dictionary, 19th edition. Wandt H, Birkmann J, Denzel T, et al. Sequential cycles of high-dose chemotherapy with dose escalation of carboplatin with or without paclitaxel supported by G-CSF mobilized peripheral blood progenitor cells: a phase I/II study in advanced ovarian cancer. Bone Marrow Transplant 1999; 23(8): 763-70. VIII. PRODUCT VARIATIONS [N] = No product variation, policy applies as stated [Y] = Standard product coverage varies from application of this policy, see below [N] CHIP POS

[N] Indemnity

[N] PPO

[N] SpecialCare

[N] HMO

[N] POS

[N] CHIP HMO

[Y] FEP HMO**

[Y] SeniorBlue*

[Y] FEP PPO**

[Y] SeniorBlue PPO* * Refer to Centers for Medicare and Medicaid Services (CMS) National Coverage Determination (NCD) 110.8.1, Stem Cell Transplantation. ** The FEP Program may include specific conditions in which autologous bone marrow transplantation may be considered eligible.

Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries, Capital Advantage Insurance Company® and Keystone Health Plan® Central. Independent licensees of the Blue Cross and Blue Shield Association. Communications issued by Capital BlueCross in its capacity as administrator of programs and provider relations for all companies.

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MEDICAL POLICY POLICY TITLE

HIGH-DOSE CHEMOTHERAPY AND HEMATOPOIETIC STEM CELL SUPPORT FOR EPITHELIAL OVARIAN CANCER

POLICY NUMBER

MP-9.017

IX.

POLICY HISTORY

MP 9.017

CAC 7/29/03 CAC 5/31/05 CAC 9/13/05 CAC 9/26/06 CAC 9/25/07 CAC 7/29/08 Policy approved for retirement effective 7/1/2009. Information added into policy 9.037 as of 7/1/2009. Effective 10/1/14- 9.037 was retired. Refer to new policy: 9.047.

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