Treatment of malignant pleural mesothelioma with cisplatin, mitomycin C and alpha interferon

Our plain-English summary of Treatment of malignant pleural mesothelioma with cisplatin, mitomycin C and alpha interferon, by S. Tansan, S. Emri, T. Selçuk, et al (Oncology, 1994).

The study

• Authors: S. Tansan, S. Emri, T. Selçuk, Y. Koç, P. Hesketh, T. Heeren, R.P. McCaffrey, Y.I. Bariş
• Journal: Oncology
• Published: 1994;51(4):348-51
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

From October 1990 to September 1991, 20 consecutive patients with histologically proven malignant pleural mesothelioma (MPM), secondary to environmental exposure to asbestos or erionite, were treated with cisplatin, mitomycin C and alpha interferon (cisplatin 50 mg/m2 i.v. on day 1 of a 21-day cycle; mitomycin C 10 mg/m2 i.v. day 1 of cycles 1,3 and 5; alpha-2b-interferon 10 x 10(6) units i.m., 4 h prior to cisplatin and 10 x 10(6) units i.v. immediately prior to cisplatin day 1 of each cycle). Eighty-two treatment cycles were administered to 19 evaluable patients. Two patients attained a partial response. Eleven patients had stable disease and 6 had disease progression. Toxicities included interferon-related fever and flu-like symptoms, and vomiting. Actuarial median survival was 15 months. Three patients are alive at 20+, 21+ and 27+ months. We conclude that while the addition of alpha interferon to cisplatin and mitomycin C did not result in an objective response higher than previously reported with the cytotoxic agents alone, the trend towards an improvement in median survival as compared to a well-matched historical group suggests some benefit from the inclusion of interferon.

In plain English

This was a phase II study, carried out in Ankara, Turkey, of a drug combination for malignant pleural mesothelioma. Between October 1990 and September 1991, 20 consecutive patients with epithelial-type mesothelioma linked to environmental asbestos or erionite exposure received cisplatin, mitomycin C and alpha-2b-interferon. One patient was lost to follow-up, leaving 19 who could be evaluated. Two had a partial response, 11 had stable disease and 6 had progressive disease. Median survival was 15 months, compared with 8 months in a historical control group matched for age, sex and mineral fiber. Overall survival did not differ significantly (p = 0.157), and the median survival difference was of borderline significance (p = 0.0564). Survival was counted from the start of therapy in the treated group and from diagnosis in the control group. There were no life-threatening side effects and no deaths from treatment. The authors concluded that adding interferon did not raise the response rate above results previously reported for cisplatin and mitomycin C alone. They added that the survival trend compared with the historical group suggested some benefit. They planned a randomized trial.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Phase II treatment study in which all patients were treated, compared with a matched historical control group
• Who was studied: 20 consecutive patients (7 male, 13 female) with symptomatic epithelial-type malignant pleural mesothelioma, entered between October 1990 and September 1991. All came from areas of Turkey where mesothelioma is endemic. 19 were evaluable. The historical control group was 19 patients with MPM treated at the same institution just before the study, matched for age, sex and mineral fiber.
• Exposure: Environmental exposure to asbestos or erionite. Among evaluable patients in each group, 16 had asbestos exposure and 3 had erionite exposure. The treatment studied was cisplatin 50 mg/m2 every 21 days, mitomycin C 10 mg/m2 every 42 days, and alpha-2b-interferon, with 6 cycles planned.
• Main results:
  • Of the 20 patients entered, 1 was lost to follow-up after one cycle, leaving 19 evaluable patients. They received 82 chemotherapy cycles in total (median 5, range 2-6).
  • Among the 19 evaluable patients, 2 had partial responses lasting 5 and 7 months, 11 had stable disease lasting 3 to 18 months, and 6 had progressive disease.
  • The objective response rate in the treated group was 10.5% (95% confidence interval 1.3-19.7%). The authors described this as not substantially different from results obtained with cisplatin and mitomycin C alone. This study had no drug-only arm.
  • Median survival for all treated patients was 15 months (range 3-27+ months). Median survival for the historical control group was 8 months.
  • Overall survival did not differ significantly between the treatment and historical control groups (log rank test, p = 0.157).
  • The difference in median survival between the control group (8 months) and the treatment group (15 months) was of borderline significance (Wilcoxon test, p = 0.0564).
  • Survival in the treated group was measured from the start of therapy. Survival in the historical control group was measured from the time of diagnosis.
  • In the treated group, the 2 patients with partial responses survived 19 and 25 months. Median survival was 17 months for those with stable disease and 6 months for those with progressive disease. 3 patients were alive at 20+, 21+ and 27+ months.
  • In the treated group there was no life-threatening toxicity and there were no toxic deaths. Interferon-related fever and flu-like symptoms occurred in all patients but were transient. Other side effects were: grade II-III nausea and vomiting in 12 patients; reversible grade II-III renal toxicity in 3; transient grade II CNS toxicity (confusion and agitation) in 1; a one-level decline in performance status in 5; and reversible grade II diarrhea in 1.
• The authors' conclusion: The authors concluded that adding alpha interferon to cisplatin and mitomycin C did not raise the objective response rate above that previously reported with the cytotoxic drugs alone. They said the trend toward longer median survival, compared with a well-matched historical group, suggests some benefit from interferon. They planned a randomized trial of cisplatin and mitomycin C with and without alpha interferon.
• Limitations the authors state:
  • The authors said the low response rate may be due to the small sample size, or to a lower dose intensity of cisplatin and mitomycin C than in an earlier trial (CALGB).
  • The authors said objective response may often be difficult to assess in malignant pleural mesothelioma because asbestos plaques or malignancy-induced fibrosis may also be present.
  • The authors noted the limitations of drawing conclusions from comparisons with a historical control group.
  • Lowest blood counts could not be measured in all patients. The reasons were travel distances between the rural villages and the treatment site in Ankara, and winter conditions.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Cisplatin, Mitomycin C, Environmental Exposure, erionite, Disease Progression, Median Overall Survival.

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• Phase II study of first-line bortezomib and cisplatin in malignant pleural mesothelioma and prospective validation of progression free survival rate as a primary end-point for mesothelioma clinical trials (European Organisation for Research and Treatment of Cancer 08052) — M.E. O'Brien, R.M. Gaafar, et al. (2013)
• Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies — V.W. Rusch, D. Niedzwiecki, et al. (1992)
• Combined systemic chemoimmunotherapy in advanced diffuse malignant mesothelioma. Report of a phase I-II study of weekly cisplatin/interferon alfa-2a — P. Soulié, P. Ruffié, et al. (1996)
• Severe electrolyte disturbances after hyperthermic intraperitoneal chemotherapy: oxaliplatin versus mitomycin C — N.M. Rueth, S.E. Murray, et al. (2011)

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