Ifosfamide sarcomas

Clinical trials showed therapeutic efficacy in a broad spectrum of tumors these include SCLC, testicular tumors, sarcomas, breast cancer, renal cell cancer, pancreatic tumors and lymphomas. Ifosfamide is less myelosuppressive than cyclophosphamide but is more toxic to the bladder. Therefore it is recommended that ifosfamide is coadministered with the thiol compound mesna to avoid hemorrhagic cystitis and to reduce the risk of developing bladder cancer. Other side effects include neurotoxicity and myelosuppression. 

Trabectedin is licensed for the treatment of advanced soft-tissue sarcoma when treatment with anthracyclines and ifosfamide has failed or is contraindicated. It is administered by intravenous infusion. Trabectedin may cause hepatobiliary disorders and for this reason hepatic function should be evaluated before starting treatment and during treatment. Dexamethasone is administered intravenously with trabectedin for its anti-emetic and hepatoprotective effects. As with other antineoplastic drugs, trabectedin causes nausea and vomiting and bone-marrow suppression as side-effects. 

Ifosfamide is active against a broad spectrum of tumors, including germ cell cancers of the testis, lymphomas, sarcomas, and carcinomas of the lung, breast, and ovary. It is thought to be more active than cyclophosphamide in germ cell cancers and sarcomas. 

Osteogenic sarcoma Doxorubicin, or methotrexate with leucovorin rescue initiated after surgery Cyclophosphamide, dacarbazine, interferon, ifosfamide plus mesna1... 

Miscellaneous sarcomas Doxorubicin plus dacarbazine Methotrexate, dactinomycin, ifosfamide plus mesna,1 vincristine, vinblastine... 

Ombrabulin (AVE8062, AC-7700) 58 (Sanofi-Aventis) is being evaluated in Phase II/III trials as a treatment for advanced stage soft tissue sarcoma for patients who have failed previous anthracycline and ifosfamide treatments.124 Ombrabulin 58125 128 is a synthetic combretastatin analogue that was licensed by Sanofi-Aventis from Ajinomoto and is also a vascular disrupting agent. 

Endometrial Ewing s sarcomao" Gastric Head and neck,squamous cell Islet cell (pancreas) Kaposi s sarcoma Doxorubicin cisplatin + cyclophosphamide CAV Cyclophosphamide (or Ifosfamide) + doxorubicin (Adriamycin) + vincristine CF epirubidri + cisplatin 5-fluorouraci1 Cisplatin + S-fluorouracil Methotrexate Screptozotocin + S-fluorouracil Etoposide or interferon affa or vinblastine ABV doxorubicin (Adriamycin) + bteomycin + vincristine or vinblastine... 

Osteogenic sarcoma Doxorubicin + cispladti + eioposide + ifosfamide... 

Ifosfamide is an alkylating agent belonging to the group of oxazaphosphorines. It is used to treat a variety of solid tumors in children, including rhabdomyosarcoma, soft tissue sarcomas, Wilms tumor, bone sarcomas, and neuroblastoma, and leukemias and lymphomas in adults. It is also sometimes used in combination with other drugs, such as doxorubicin or cisplatin and etoposide. 

The effects of second-trimester or third-trimester exposure to ifosfamide are poorly documented, although normal children have been described (14). In a 17-year-old pregnant woman with Ewing s sarcoma doxorubicin and ifosfamide during the 25th to 30th weeks of gestation did not affect the child, which was delivered at 32 weeks (15). 

Stuart-Elarris R, Elarper PG, Kaye SB, and Wlltsaw E. Ellgh-dose Ifosfamide by Infusion with mesna In advanced soft tissue sarcoma. CancerTreat Rep 10[suppA] 163-164,1988... 

Stuart-Elarris RC, Elarper PJ, Parson CAand coll. Ellgh-dose alkylation therapy using Ifosfamide infusion with Mesna in the treatment of adult soft-tissue sarcoma. Cancer Chemother Pharmacol, 11 69-74,1983... 

Stuart-Harris R, Harper PG, Kaye SB, Wiltsaw E. High-dose ifosfamide by infusion with mesna in ad-vanced soft tissue sarcoma. Cancer Treat Rep 1988 10(suppl A) 163-164. 

Stuart-Harris RC, Harper PG, Parsons CA, Kaye SB, Mooney CA, Gowing NF, Wiltshaw E. High-dose all lation therapy using ifosfamide infusion with mesna in the treatment of adult advanced soft-tissue sarcoma. Cancer Chemother Pharmacol 1983 ... 

Etoposide is used primarily in treatment of testicular tumors in combination with bleomycin and cispiatin, and in combination with cispiatin and ifosfamide for small-cell carcinoma of the lung. It also is active against non-Hodgkin s lymphomas, acute nonlymphocytic leukemia, and Kaposi s sarcoma associated with AIDS. Etoposide has a favorable toxicity profile for dose escalation in that its primary acute toxicity is myelosuppression. In combination with ifosfamide and carboplatin, it is frequently used for high-dose chemotherapy in total doses of 1500 to 2000 mg/m. ... 

In summary, ifosfamide, an alkylating agent with anti-neoplastic properties (1.2 g/mVday fV for 5 days), is indicated in the treatment of testicular cancer. In addition, ifosfamide has been used in lung cancer, Hodgkin s and non-Hodgkin s lymphoma, breast cancer, acute and chronic lymphocytic leukemia, ovarian cancer, and sarcomas. 

This potent anticancer drug is now widely used in chemotherapy in association with several other drugs (e.g., vinblastine, methotrexate, carboplatine, ifosfamide, or etoposide) in the treatment of Hodgkin s disease (9), of head and neck cancers (JO, 11), of disseminated germ cell tumors (12), and of poor-prognosis epidemic Kaposi s sarcoma (13) (for previous articles on the clinical use of BLM, see references listed in Refs. 9-13). 

The most important clinical use of vinblastine is with bleomycin and cisplatin (see below) in the curative therapy of metastatic testicular tumors, although it has been supplanted by etoposide or ifosfamide in this disease. It is a component of the standard curative AB VD regimen for Hodgkin s disease (adriamycin, bleomycin, vinblastine, and dacarbazine). It also is active in Kaposi s sarcoma, neuroblastoma, and histiocytosis X, and in carcinoma of the breast and choriocarcinoma. 

Mir O, Berrada N, Domont J, CiofB A, Boulet B, Terrier P, et al. Doxorubicin and ifosfamide for high-grade sarcoma during pregnancy. Cancer Chemother Pharmacol 2012 69(2) 357-67. 

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