Combination chemotherapy with mitoxantrone, methotrexate, and mitomycin (MMM regimen) in malignant pleural mesothelioma: a phase II study

Our plain-English summary of Combination chemotherapy with mitoxantrone, methotrexate, and mitomycin (MMM regimen) in malignant pleural mesothelioma: a phase II study, by C. Pinto, A. Marino, M. Guaraldi, et al (American Journal of Clinical Oncology, 2001).

The study

• Authors: C. Pinto, A. Marino, M. Guaraldi, B. Melotti, E. Piana, A. Martoni, F. Pannuti
• Journal: American Journal of Clinical Oncology
• Published: 2001;24(2):143-7
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The prognosis of malignant pleural mesothelioma is poor, with a median survival time from diagnosis of 7 to 17 months. At present there is no standardized treatment of this neoplasia. Between July 1995 and January 1999, 22 patients with malignant pleural mesothelioma were enrolled in our study. The characteristics of patients were: 16 men and 6 women; median age 61 years (range, 49-77 years); stage (according to Butchart): 8 patients stage I, 10 stage II, 2 stage III, and 2 stage IV; cytologic diagnosis in 5 cases and histologic diagnosis in 17 cases. The treatment consisted of mitoxantrone 10 mg/m2 intravenous (IV) or intrapleural (IPL), methotrexate 35 mg/m2 IV, and mitomycin 7 mg/m2 IV on day 1 and repeated every 3 weeks, with mitomycin in alternate cycles (MMM regimen). One complete response (4.5%) (42 months of duration) and 6 partial responses (27.3%) (5, 5, 7, 9, 14, and 19 months of duration) were achieved; the overall response rate (ORR) was 31.8% (95% CI, 12.4-51.3%); 7 patients were stable under this treatment (31.8%). According to the pathologic type, ORR for the only epithelial type was 39.9% (95% CI, 15.2-64.8%). Median time to progression was 6 months (range, 1-22). The overall median survival time was 13.5 months (range, 1-50); the median survival time of responders significantly differed from that of nonresponders (18.0 versus 8.5 months; p = 0.017). This treatment produced a considerable clinical benefit, with improvement of dyspnea (68.4%) and pain (33.3%); 15 of 19 patients (78.9%) with pleural effusion at the time of diagnosis showed an important reduction in pleural fluid during chemotherapy. Hematologic toxicity was the main side effect; World Health Organization grade III to IV of neutropenia, anemia, and thrombocytopenia were observed in 81.8%, 13.6%, and 22.7% of patients, respectively. From the data presented here, this regimen can be considered active in the treatment of malignant pleural mesothelioma.

In plain English

This phase II trial at a hospital in Bologna, Italy, tested a chemotherapy combination, the MMM regimen (mitoxantrone, methotrexate and mitomycin), in 22 patients with malignant pleural mesothelioma enrolled from July 1995 to January 1999. Asbestos exposure was proven in 11 of the 14 patients whose exposure data were judged adequate. One patient (4.5%) had a complete response lasting 42 months, and 6 (27.3%) had partial responses, for an overall response rate of 31.8% (95% CI, 12.4 to 51.3%). Among patients with the epithelial type, the response rate was 39.9% (95% CI, 15.2 to 64.8%). Overall median survival was 13.5 months. Responders had a median survival of 18.0 months, versus 8.5 months for nonresponders. Breathlessness improved in 13 of 19 patients and pain in 3 of 9. Fluid around the lung was reduced in 15 of 19 patients who had it. The main side effect was neutropenia, a fall in neutrophils (a type of white blood cell). It was grade IV in 13 patients (59.1%) and grade III in 5 (22.7%). The authors concluded that the regimen was an active and tolerable treatment.

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: Single-institution phase II clinical trial with a two-step design
• Who was studied: 22 patients with malignant pleural mesothelioma (16 men, 6 women; median age 61 years, range 49–77) enrolled between July 1995 and January 1999 at S. Orsola-Malpighi Hospital, Bologna, Italy
• Exposure: The treatment studied was the MMM chemotherapy regimen. It consisted of mitoxantrone 10 mg/m2 given intravenously or into the pleural space, methotrexate 35 mg/m2 intravenously, and mitomycin 7 mg/m2 intravenously on day 1, repeated every 3 weeks, with mitomycin in alternate cycles. No asbestos fiber types were reported.
• Main results:
  • Asbestos exposure was proven in 11 of the 14 patients (78.6%) for whom exposure data were considered adequate. There were no exposure data for 8 patients.
  • All 22 patients: 1 complete response (4.5%, 42 months' duration) and 6 partial responses (27.3%), for an overall response rate of 31.8% (95% confidence interval, 12.4–51.3%)
  • 7 patients (31.8%) had stable disease (no change). In 8 patients (36.4%) the disease progressed without prior stabilization.
  • Epithelial type: overall response rate 39.9% (95% confidence interval, 15.2% to 64.8%)
  • Median time to progression for the whole group was 6 months (range, 1–22 months)
  • Overall median survival was 13.5 months (range, 1–50 months)
  • Median survival was 18.0 months in responders versus 8.5 months in nonresponders (p = 0.017). The authors reported this difference as statistically significant.
  • Dyspnea (breathlessness) improved in 13 of 19 patients (68.4%) and pain in 3 of 9 (33.3%)
  • 15 of 19 patients (78.9%) with pleural effusion at diagnosis showed a reduction in pleural fluid during chemotherapy
  • Neutropenia was the most severe toxicity: grade IV in 13 patients (59.1%) and grade III in 5 patients (22.7%). Dose reduction for myelosuppression was needed in 12 patients (54.5%).
• The authors' conclusion: The authors concluded that, from their data, the MMM regimen is an active and tolerable treatment in malignant pleural mesothelioma

Topics

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

Medical terms in this study, explained in our Lexicon: Chemotherapy, Pleural Mesothelioma, Prognosis, Median Survival, Dyspnea, Pleural Effusion, Neutropenia.

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