Summary
Forty three patients with histologically confirmed malignant mesothelioma were entered onto an Eastern Cooperative Oncology Group phase II study of ifosfamide given with mesna. Eligibility criteria included adequate performance status, hemogram and renal functions.
Ifosfamide was given at 1.5 g/m2 in 200 ml of normal saline over 30 minutes by intravenous infusion on days 1 to 5 of each 21 day cycle. Mesna was given at 300 mg/m2 on each day of ifosfamide at 0,4 and 8 hours.
Two patients were cancelled and one patient was ineligible. The most common toxicity was haematologic. More than 50% of the patients had at least one episode of severe or life threatening toxicity and 2 patients had lethal toxicity (1 renal and 1 pulmonary oedema attributed to treatment), and an additional 4 patients died while on study (2 of cardiac and 2 of cerebral vascular disease not considered directly related to treatment).
Of the 40 eligible patients one was unevaluable for response, and one patient had a partial response lasting 6.3 months. Twenty four patients had a no change status with a median duration of 5 months. The median time to treatment failure for all eligible patients was 2.5 months. The median overall survival time (from registration) for all eligible patients was 6.9 months. In multi variable models, factors that predicted for a statistically significant poorer survival were age ≥ 62, stage ≥3, performance status poorer than 0 to 1 and prior surgery (i.e.: more than biopsy).
The severe toxicity, documented in more than half of the patients, precludes any further dose escalation of ifosfamide in these patients. With only one response among 39 evaluable patients, it is concluded, from this extended phase II trial, that ifosfamide does not have a worthwile therapeutic effect in patients with malignant mesothelioma.
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References
Alberts AS, Falkson G, Goedhals L, Vorobiof DA, van der Merwe CA: Malignant Pleural Mesothelioma: A disease unaffected by current therapeutic maneuvers. J Clin Oncol 6:527–535, 1988
Wörn H: Möglichkeiten und ergebnisse der chirurgischen behandlung des malignen pleuramesothelioms. Thoraxchirurgie 22:391–393, 1974
Butchart EG, Ashcroft T, Barnsley WC, Holden MP: Pleuroopneumocectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. Thorax 31:15–24, 1976
DaVille MJ, Faber LP, Kittle CF, Jensik RJ: Extrapleural pneumonectomy for diffuse malignant mesothelioma. Ann Thorac Surg 42:612–618, 1986
DeLaria GA, Jensik R, Faber LP, Kittle CF: Surgical management of malignant mesothelioma. Ann Thorac Surg 26:3785–382, 1986
Rusch V, Holmes EC (For the Lung cancer study group [LCSG]): Extra-pleural pneumocectomy (EPP) for malignant mesothelioma. Lung Cancer 4 (Suppl):A83 (Abst 5.16), 1988
Law MR, Gregor A, Hodson ME, Bloom HJG, Turner-Warwick M: Malignant mesothelioma of the pleura: a study of 52 treated and 64 untreated patients. Thorax 39:255–259, 1984
Martini N, Bains M, Beattie EJ: Indications for pleurectomy in malignant effusion. Cancer 35:734–738, 1975
Ball DL, Cruickshank DG: The treatment of malignant mesothelioma of the pleura: Review of a 5-year experience, with special reference to radiotherapy. Am J Clin Oncol (CCT) 13:4–9, 1990
Falkson G, Alberts AS, Falkson HC: Malignant pleural mesothelioma treatment: the current state of the art. Cancer Treat Rev 15:231–242, 1988
Harvey VJ, Slevin ML, Ponder BAJ, Blackshaw AJ, Wrigley PFM: Chemotherapy of diffuse malignant mesothelioma: Phase II trials of single agent 5-fluorouracil and adriamycin. Cancer 54:961–964, 1984
Sorenson PG, Bach F, Bork E, Hansen HH: Randomized trial of doxorubicin versus cyclophosphamide in diffuse malignant pleural mesothelioma. Cancer Treat Rep 69:1431–1432, 1985
Mintzer DM, Kelsen D, Frimmer D, Heelan R, Gralla R: Phase II trial of high dose cisplatin in patients with malignant mesothelioma. Cancer Treat Rep 69:711–712, 1985
Kelsen D, Gralla R, Cheng E, Martini N: Vindesine in the treatment of malignant mesothelioma: A phase II study. Cancer Treat Rep 67:821–822, 1983
Eisenhauer EA, Evans WK, Raghaven D, Desmeules MJ, Murray NR, Stuart-Harris R, Wilson KS: Phase II study of mitoxantrone in patients with mesothelioma. A National Cancer Institute of Canada Clinical Trials Group Study. Cancer Treat Rep 70:1029–1030, 1986
Cantwell BMJ, Earnshaw M, Harris AL: Phase II study of a novel antifolate n10-propargyl-5,8 dideazafolic acid (CB3717), in malignant mesothelioma. Cancer Treat Rep 70:1335–1336, 1986
Gatzemeier U, Calavrezos A, Kaukel E, Koschel G, Maghussen H, Radenbach D: The new anthracycline THP- ADM (4′-0-tetrahydropyrnyl-adriamycin) in the treatment of malignant pleural mesothelioma. Presented at the 18th National Cancer Congress of the German Cancer Society, 1986. J Cancer Res Clin Oncol 111 (Suppl) 6: 1986. (Abstract)
Dhingra HM, Murphy WK, Winn RJ, Raber MN, Hong WH: Phase II trial of 5,6-dihydro-5-azacytidine in pleural malignant mesothelioma. Invest New Drugs 9:69–72, 1991
van Breukelen FJM, Mattson K, Giaccone G, van Zandwijk N, Planteydt HT, Kirkpatrick A, Dalesio O: Mitoxantrone in malignant pleural mesothelioma: A study by the EORTC Lung Cancer Cooperative Group. Eur J Cancer 27:1627–1629, 1991.
Lerner IIJ, Schoenfeld DA, Martin A, Falkson G, Borden E: Malignant mesothelioma: The Eastern Cooperative Oncology Group (ECOG) experience. Cancer 52:1981–1985, 1983
van Dyk JJ, Falkson HC, van der Merwe AM, Falkson G: Unexpected toxicity in patients treated with iphosphamide. Cancer Res 32:921–924, 1972
Falkson G, van Dyk JJ, Stapelberg R, Falkson HC: Mesnum as a protector against kidney and bladder toxicity with high-dose ifosfamide treatment. Cancer Chemother Pharmacol 9:81–84, 1982
Alberts AS, Falkson G, van Zyl L: Malignant pleural mesothelioma: Phase II pilot study of ifosfamide and mesna. (Letter) Jnl Nat Cancer Inst 80:698–700, 1988
Oken MM, Creech LH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP: Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol (CCT) 5:649–655, 1982
Kaplan EL, Meier P: Non parametric estimation from incomplete observations. Journal of the Am Stat Assoc 58:457–481, 1958
Peto R, Peto J: Asymptotically efficient rank invariant test procedures. Journal of the Royal Statistical Society, Series A 135:185–198, 1972
Cox DR: Regression models and life tables (with discussion) Journal of the Royal Stat Soc, Series B, 34:187–220, 1972.
Zidar B, Metch B, Militello L, Balcerzak S, Pierce H: A Phase II evaluation of ifosfamide and mesna in unresectable diffuse malignant mesothelioma: A Southwest Oncology Group (SWOG) study. Amer Soc Clin Oncol 10:350, 1991 (Abstract #1245)
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Falkson, G., Hunt, M., Borden, B.C. et al. An extended phase II trial of ifosfamide plus mesna in malignant mesothelioma. Invest New Drugs 10, 337–343 (1992). https://doi.org/10.1007/BF00944192
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DOI: https://doi.org/10.1007/BF00944192