Summary
The object of the study was to evaluate the effectiveness of ifosfamide/etoposide and mesna therapy in advanced breast cancer. A total of 44 patients with breast cancer were included in the trial. Eligibility criteria included measurable, refractory disease; prior anthracycline therapy (or its contraindication); a life expectancy of at least 3 months; and adequate hepatic, renal, CNS and bone marrow function. All patients were≤70 years of age and had a Karnofsky performance status of≥50%. There were 36 evaluable cases. Sites of metastatic disease included bone (19), skin (18), liver (9), lung (14), lymph node (19), and miscellaneous (7). Treatment consisted of 1,500 mg/m2 ifosfamide given i.v. on days 1–5, 120 mg/m2 etoposide given i.v. on days 1–3, and 400 mg i.v. mesna given with and at 4 and 8 h after ifosfamide. Cycles were repeated every 28 days. Initial doses were reduced by 25% or 50% in patients who had previously undergone both chemotherapy and radiotherapy. A median of 4 cycles (range, 2–8) were given. The myelotoxicity was marked: WHO grades 3/4 leukopenia (n=37), grades 3/4 thrombocytopenia (n=12), and grades 2/3 anemia (n=13). Due to myelotoxicity, dose reduction or prolongation of treatment-free intervals was necessary in 28 cases. Alopecia was seen in 35 patients and CNS toxicity, in 8. Partial remission (PR) was obtained in five cases and complete remission (CR), in three. Sites of response included the lung (5), skin (4), lymph node (5), and peritoneum (1). The duration of response was 4 (n=2) and 8 (n=1) months for CR and 2 (n=2), 6 (n=2), and 10 (n=1) months for PR. We conclude that the ifosfamide/etoposide and mesna regimen is effective, but its myelotoxicity is treatment-limiting.
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References
Ahmann DL, Bisel HF, Hahn RG (1974) Phase II clinical trial of isophosphamide (NSC-109724) in patients with advanced breast cancer. Cancer Chemother Rep 58: 861
Becher R, Höfeler H, Kloke O, Kurschel E, Schilcher RB, Weinhardt O, Wandl U, Schmidt CG (1989) Ifosfamide, methotrexate, and 5-fluorouracil in advanced pretreated breast cancer. Semin Oncol 16 [Suppl 3]: 56
Brade WP, Herdrich K, Varini M (1985) Ifosfamide — pharmacology, safety and therapeutic potential. Cancer Treat Rev 12: 1
Brambilla C, Delena M, Rossi A, Valagussa P, Bonadonna G (1976) Response and survival in advanced breast cancer after two noncross-resistant combinations. Br Med J 1: 801
Bramwell VHC, Mouridsen HT, Santoro A, Blackledge G, Somers R, Verwey J, Dombernowsky P, Onsrud M, Thomas D, Sylvester R, Oosterom A van (1987) Cyclophosphamide versus ifosfamide: final report of a randomized phase II trial in adult soft tissue sarcoma. Eur J Cancer Clin Oncol 23: 311
Brema F, Porcile GF, Parodi GC (1977) Clinical evaluation of isophosphamide in solid epithelial advanced tumors. Clin Pharmacol Ther 5: 122
Burkert H (1982) Ifosfamide: European perspective. Semin Oncol 4 [Suppl 1]: 28
Buzdar AU, Legha SS, Tashima CK, Yap HY, Hortobagyi GN, Hersch EM, Blumenschein GR, Bodey PG (1979) Ifosfamide versus cyclophosphamide in combination drug therapy for metastatic breast cancer. Cancer Treat Rep 63: 115
Cabanillas F, Hagemeister FB, Bodey GP, Freireich EJ (1982) IMVP-16, an effective regimen for patients with lymphoma who have relapsed after initial combination chemotherapy. Blood, 60: 693
Cavalli F, Jungi WF, Brunner KW (1981) Randomisierte Phase-II-Studie mit VP-16-213 (Etoposide) in der Behandlung des fortgeschrittenen Mammakarzinoms Onkologie, 4: 80
Drings P (1989) European experience with ifosfamide in non-small-cell lung cancer. Semin Oncol 16 [Suppl 3]: 22
Einhorn LH (1989) Ifosfamide in small cell lung cancer. Semin Oncol 16 [Suppl 3]: 19
Einhorn LH, Loehrer PJ (1986) Ifosfamide chemotherapy for pancreatic cancer. Cancer Chemother Pharmacol 18 [Suppl 2]: 51
Falkson G (1977) Clinical experience with ifosfamide at various dose ranges and in combination with VP 16-213. In: Proceedings of the International Holoxan Symposium, Düsseldorf, 21–23 March, 1977, pp 168–170
Falkson G, Falkson HC (1976) Further experience with isophosphamide. Cancer Treat Rep 60: 955
Gad-El-Mawla N, Hamza MR, El Serafi M (1984) Ifosfamide, methotrexate, and fluorouracil — effective combination in refractory breast cancer. J Egypt Natl Cancer Inst 1: 81
Goldin A (1982) Ifosfamide in experimental tumor systems. Semin Oncol 4 [Suppl 1]: 14
Hayward IL, Carbone PP, Heuson IC, Kumaoka S, Segaloff A, Rubens RD (1977) Assessment of response to therapy in advanced breast cancer. Cancer 39: 1289
Henderson IC, Hayes DF, Come S, Harries IR, Canellos G (1987) New agents and new medical treatments for advanced breast cancer. Semin Oncol 1: 34
Hunter HL, Harrison EF (1982) The anticancer spectrum of ifosfamide. Semin Oncol 4 [Suppl 1]: 96
Meanwell CA, Blake EB, Kelly KA, Honigsberger L, Blackledge G (1986) Prediction of ifosfamide/mesna associated encephalopathy. Eur J Cancer Clin Oncol 22: 815
Rodriguez V, McCredie KB, Keating MJ, Valdivieso M, Bodey GP, Freireich EJ (1978) Ifosfamide therapy for hematological malignancies in patients refractory to prior treatment. Cancer Treat Rep 62: 493
Rodriguez V, Cabanillas F, Bodey P, Freireich EJ (1982) Studies with ifosfamide in patients with malignant lymphoma. Semin Oncol 4 [Suppl 1]: 87, 101
Salmon SE, Jones SE (1979) Studies of the combination of Adriamycin and cyclophosphamide (alone or with other agents) for the treatment of breast cancer. Oncology 36: 40
Thatcher N, Cerny T, Stout R, Anderson H, Barber PV, Wolstenholme RI, Barnes P, Deiraniya A (1987) Ifosfamide, etoposide, and thoracic irradiation therapy in 163 patients with unresectable small cell lung cancer. Cancer 60: 2382
Vaughn CB, Panettiere F, Thigpen T, Bottomley R, Hoogstraten B, Samal B (1981) Phase II evaluation of VP-16-213 in patients with advanced breast cancer: a Southwest Oncology Group study. Cancer Treat Rep 65: 443
Wheeler BJ, Loehrer PJ, Williams SD, Einhorn LH (1986) Ifosfamide in refractory male germ cell tumors. J Clin Oncol 4: 28
Williams M (1984) Ifosfamide in the treatment of advanced breast cancer. In: Proceedings: ifosfamide in solid tumors Boehringer Ingelheim, Croydan, England, p 32
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Manegold, C., Worst, P., Bickel, J. et al. Ifosfamide/etoposide and mesna uroprotection in advanced breast cancer. Cancer Chemother. Pharmacol. 26 (Suppl 1), S87–S90 (1990). https://doi.org/10.1007/BF00685431
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DOI: https://doi.org/10.1007/BF00685431