Weekly systemic combination of cisplatin and interferon alpha 2a in diffuse malignant pleural mesothelioma

Our plain-English summary of Weekly systemic combination of cisplatin and interferon alpha 2a in diffuse malignant pleural mesothelioma, by A. Purohit, L. Moreau, A. Dietemann, et al (Lung Cancer, 1998).

The study

• Authors: A. Purohit, L. Moreau, A. Dietemann, R. Seibert, G. Pauli, J.M. Wihlm, E. Quoix
• Journal: Lung Cancer
• Published: 1998;22(2):119-25
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The treatment of diffuse malignant pleural mesothelioma (DMPM) remains grim. Neither surgery, radiotherapy nor chemotherapy can be considered as a standard therapy. Immunotherapy with interferon (IFN) in combination with chemotherapy may be an interesting new approach. In 13 consecutive patients with DMPM, we used a weekly combination of cisplatin (CDDP) (60 mg/m2; day 2) and IFN alpha 2a (6 MU/day; days 1-4) in a protocol of two cycles of 4 weeks on/4 weeks off followed by 3 weeks on/3 weeks off. Total treatment duration was thus 25 weeks. In responders, IFN as maintenance monotherapy was continued for a further 6 months. There were nine males and four females with an average age of 65.3 years (range 51-72 years). Eleven had epithelial, one had mixed and one had a sarcomatoid form of DMPM. Five patients were classified as stage II, six as stage III and two as stage IV, as per the International Mesothelioma Interest Group. Thirty-five cycles were administered with a median of three cycles/patient (range 0.75-4). The median total cumulative dose of CDDP was 596 mg/m2 (range 114-861) and that of IFN alpha 2a was 264 MU (range 72-336). Four patients received IFN maintenance therapy, one for 3 months and three for 6 months. One patient had a complete response, four had a partial response, six had a stable disease and the disease progressed in one. One patient was non evaluable for response. All patients were assessable for toxicity. Hematological toxicity was the most frequently observed but was manageable (grade 3 anemia in five patients, grade 3 thrombocytopenia in three patients, grade 3 neutropenia in five patients). Grade 1 renal toxicity was observed in six patients, grade 2-3 asthenia in six patients and an average 5-kg weight loss was noted in nine patients. In conclusion, systemic combination of CDDP and IFN alpha 2a in large doses is effective at the expense of non-negligible toxicity.

In plain English

This French study described 13 consecutive, previously untreated patients with diffuse malignant pleural mesothelioma treated in Strasbourg from December 1993 to July 1997. Ten had a history of occupational or environmental asbestos exposure. During treatment weeks, patients received cisplatin (60 mg/m2) and interferon alpha 2a (6 million units daily on four days), in four cycles separated by rest periods over a planned 25 weeks. Five patients completed all four cycles. Of 12 patients assessable for response, one had a complete response, four a partial response, six stable disease and one progressed. Median survival was 16.5 months (confidence interval 10.4 to 30.3) and median time to progression 6.4 months (4.6 to 11.8). Blood-related side effects were most common, including grade 3 anemia and neutropenia in five patients each. Six patients had asthenia (weakness and fatigue); nine lost an average of 5 kg. Non-blood side effects ended treatment in two patients. The authors concluded that the large-dose combination was feasible. They added that raising interferon from 3 to 6 million units a day did not seem to improve results. They noted the small number of patients.

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: Small single-centre treatment study (uncontrolled series of consecutive patients) of combined cisplatin and interferon alpha 2a
• Who was studied: 13 consecutive, previously untreated patients with histologically and immunohistochemically confirmed malignant pleural mesothelioma, Strasbourg university hospitals, France, December 1993 to July 1997. Nine were male, with a mean age of 65.3 years (range 51 to 72). By tissue type, 11 were epithelial, one mixed and one fusiform. By stage, five were stage II, six stage III and two stage IV.
• Exposure: Treatment studied: cisplatin 60 mg/m2 on day 2 of each treatment week, plus interferon alpha 2a 6 MU/day given under the skin on days 1 to 4. The planned course was four cycles over 25 weeks, with rest periods between cycles: two cycles of 4 treatment weeks, then two cycles of 3 treatment weeks. Responders could continue interferon alone. Patients were also asked about their occupations to assess possible asbestos exposure.
• Main results:
  • 10 of the 13 patients had a history of occupational or environmental exposure to asbestos
  • Five of the 13 patients completed all four treatment cycles
  • Of 12 patients assessable for response: one complete response, four partial responses, six stable disease, one progression. One patient was not evaluable because a CT scan was omitted.
  • For all patients, median survival was 16.5 months (CI 10.4 to 30.3) and median time to progression was 6.4 months (CI 4.6 to 11.8)
  • Blood-related toxicity was the most frequent, with grade 3 anemia in five patients, grade 3 thrombocytopenia in three and grade 3 neutropenia in five
  • Gastrointestinal toxicity occurred in six patients (46%) and stopped treatment in one. Acute pulmonary edema in another patient led to the last cycle being omitted. In total, non-blood toxicity stopped treatment in two patients.
  • Six patients had asthenia (grade 3 in four, grade 2 in two), and nine patients lost an average of 5 kg of weight (range 1 to 9 kg)
  • Six patients showed symptom improvement; chest pain disappeared in five of seven patients who had it
• The authors' conclusion: The authors concluded that the combination of cisplatin and interferon in large doses was feasible. They also concluded that raising the interferon dose from 3 to 6 MU/day did not seem to increase toxicity but also did not give better results. Their abstract states that the combination is effective at the expense of non-negligible toxicity.
• Limitations the authors state:
  • The number of patients was small

Topics

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

Medical terms in this study, explained in our Lexicon: Cisplatin, Pleural Mesothelioma, Chemotherapy, Immunotherapy, Sarcomatoid, Mesothelioma, Cumulative Dose, Neutropenia.

Related studies

• 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)
• Treatment of malignant pleural mesothelioma with cisplatin, mitomycin C and alpha interferon — S. Tansan, S. Emri, et al. (1994)
• Effects of natural interferon alpha, natural tumor necrosis factor alpha and their combination on human mesothelioma xenografts in nude mice — T. Ohnuma, L. Szrajer, et al. (1993)
• Safety, feasibility and therapeutic activity of intrapleural autologous lymphocyte conditioned medium followed by systemic recombinant interleukin-2 and interferon-alpha in a patient with malignant pleural mesothelioma — S. Duensing, H. Hamm, et al. (1997)
• Interferon (IFN)-alpha and IFN-gamma in combination with methotrexate: in vitro sensitivity studies in four human mesothelioma cell lines — A. Hand, K. Pelin, et al. (1995)
• Interferon-alpha and -gamma in combination with chemotherapeutic drugs: in vitro sensitivity studies in four human mesothelioma cell lines — A.M. Hand, K. Husgafvel-Pursiainen, et al. (1992)

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