Randomized comparison of cyclophosphamide, imidazole carboxamide, and adriamycin versus cyclophosphamide and adriamycin in patients with advanced stage malignant mesothelioma: a Sarcoma Intergroup Study

Our plain-English summary of Randomized comparison of cyclophosphamide, imidazole carboxamide, and adriamycin versus cyclophosphamide and adriamycin in patients with advanced stage malignant mesothelioma: a Sarcoma Intergroup Study, by M.K. Samson, L.P. Wasser, E.C. Borden, et al (Journal of Clinical Oncology, 1987).

The study

• Authors: M.K. Samson, L.P. Wasser, E.C. Borden, H.J. Wanebo, R.H. Creech, M. Phillips, L.H. Baker
• Journal: Journal of Clinical Oncology
• Published: 1987;5(1):86-91
• Type of article: Randomized trial
• Cited by: 58 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In 1980, a consensus chemotherapy intergroup study for advanced malignant mesothelioma was initiated based on a collaborative agreement among the Eastern Cooperative Oncology Group (ECOG), the Southwest Oncology Group (SWOG), and the Southeastern Cancer Study Group (SECSG). The purpose of the study was to evaluate cyclophosphamide (500 mg/m2 day 1), imidazole carboxamide (250 mg/m2 days 1 through 5), and doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) (50 mg/m2 day 1) v cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) in a randomized prospective clinical trial involving 76 fully evaluable patients with advanced stages II to IV malignant mesothelioma. A total of nine responses (12%) were documented, including three complete and six partial responses. There was no significant difference in response duration or survival between treatment arms. Leukopenia (greater than 2,000/microL) was observed in 46% of patients treated with the three-drug combination and 38% of patients receiving the two-drug combination. The variables of performance status 0-1 and the absence of prior chemotherapy/radiotherapy were significant with respect to favorable impact on survival. We conclude, based on the minimal benefit observed, that the combination of cyclophosphamide and doxorubicin with or without imidazole carboxamide does not warrant further investigation in patients with advanced-stage malignant mesothelioma.

In plain English

This randomized trial by three cooperative groups (ECOG, SWOG and SECSG) compared two chemotherapy combinations in advanced (stage II to IV) malignant mesothelioma of the pleura or peritoneum. Of 96 patients entered between 1980 and 1984, 76 were fully evaluable. Patients received either cyclophosphamide, imidazole carboxamide and doxorubicin (Adriamycin), called CIA, or cyclophosphamide and doxorubicin, called CA. Overall, 9 patients (12%; 95% confidence limits 6% to 21%) responded: 3 completely and 6 partially. Response rates were 13% with CIA and 11% with CA, not significantly different. Median survival was 25 weeks with CIA and 30 weeks with CA, not a statistically significant difference. Good performance status and no prior chemotherapy or radiotherapy were linked to longer survival, but in a model accounting for all variables only the latter was a significant independent factor. Grade 3 or worse leukopenia (low white cell count) occurred in 46% of CIA and 38% of CA patients. Two CA patients developed nonfatal heart muscle disease; no deaths were drug-related. The authors concluded that, given the minimal benefit, these combinations did not warrant further investigation.

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: Prospective randomized clinical trial (multicenter cooperative group chemotherapy trial)
• Who was studied: 96 patients entered between 1980 and 1984 by three cooperative groups (49 ECOG, 32 SWOG, 15 SECSG). All had pleural or peritoneal malignant mesothelioma at advanced stage (II to IV). 20 were ineligible or inevaluable, leaving 76 fully evaluable patients.
• Exposure: This study compared chemotherapy treatments; it was not a study of asbestos exposure. CIA was cyclophosphamide 500 mg/m2 and doxorubicin 50 mg/m2 intravenously on day 1, plus imidazole carboxamide 250 mg/m2 intravenously on days 1 to 5. CA used the same doses of cyclophosphamide and doxorubicin. Cycles were repeated at 21-day intervals.
• Main results:
  • Among all 76 evaluable patients, there were 9 responses (3 complete, 6 partial), an overall response rate of 12% (95% confidence limit, 6% to 21%).
  • Among the 45 patients with measurable disease, 7 responded (16%).
  • Response rates were 13% for CIA-treated patients and 11% for CA-treated patients, with no significant difference between the two combinations.
  • Median duration of response was 20 weeks (range 8 to 41) with the three-drug combination (CIA) and 30 weeks (range 15 to 156) with the two-drug combination (CA).
  • In CIA-treated patients, median relapse-free interval was 9 weeks and median survival was 25 weeks.
  • In CA-treated patients, median relapse-free interval was 14 weeks and median survival was 30 weeks. The differences between the arms were not statistically significant.
  • Performance status 0 to 1 and absence of prior chemotherapy or radiotherapy were associated with longer survival. In a Cox model accounting for all variables, only absence of prior chemotherapy or radiotherapy was a statistically significant independent variable.
  • Grade 3 or greater leukopenia (white count below 2,000 per microliter) developed in 46% of CIA patients and 38% of CA patients.
  • Major nonhematologic toxicities (nausea, vomiting, stomatitis and/or diarrhea) occurred in 85% of patients on the three-drug combination and 67% of patients on the two-drug combination.
  • Two CA-treated patients developed nonfatal congestive cardiomyopathy attributed to their drug therapy. There were no drug-related deaths.
• The authors' conclusion: The authors concluded that, given the minimal benefit observed, cyclophosphamide and doxorubicin with or without imidazole carboxamide does not warrant further investigation in advanced-stage malignant mesothelioma, and that new treatment strategies are needed.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Sarcoma, Chemotherapy, Doxorubicin, Clinical Trial, Performance Status.

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