High-dose doxorubicin, dexrazoxane, and GM-CSF in malignant mesothelioma: a phase II study-Cancer and Leukemia Group B 9631

Our plain-English summary of High-dose doxorubicin, dexrazoxane, and GM-CSF in malignant mesothelioma: a phase II study-Cancer and Leukemia Group B 9631, by M.P. Kosty, J.E. Herndon, N.J. Vogelzang, et al (Lung Cancer, 2001).

The study

• Authors: M.P. Kosty, J.E. Herndon, N.J. Vogelzang, H.L. Kindler, M.R. Green
• Journal: Lung Cancer
• Published: 2001;34(2):289-95
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Doxorubicin is the most widely studied agent for the treatment of malignant mesothelioma. In conventional doses, the response rate is approximately 17%. Higher dose doxorubicin has been successfully employed in other tumor types. Dexrazoxane has been demonstrated to reduce the cardiac toxicity associated with long term, chronic use of doxorubicin. Based upon phase I data generated by the Cancer and Leukemia Group B (CALGB) indicating that doxorubicin at a dose of 120 mg/m(2) when combined with dexrazoxane and GM-CSF could be safely administered, the CALGB undertook a phase II study of high-dose doxorubicin in patients with malignant mesothelioma. Toxicity was excessive, necessitating protocol modification and ultimately protocol termination. There were no objective responses observed. We conclude that high-dose doxorubicin administered with dexrazoxane is unacceptably toxic in this patient population.

In plain English

This phase II trial by the Cancer and Leukemia Group B (CALGB 9631) tested high-dose doxorubicin, a chemotherapy drug, in patients with malignant mesothelioma. It was given with dexrazoxane, meant to protect the heart, and GM-CSF, a blood-cell growth factor. Ten patients were enrolled between November 1996 and March 1997, out of 33 planned. Six were recorded as asbestos-exposed, one as not, and three as unknown. The doxorubicin dose started at 120 mg/m2 but was lowered to 90 mg/m2 after severe toxicity in the first patient. No patient had a tumor response: five had stable disease, one progressed, and four could not be assessed. Median overall survival was 4.8 months, with 20% alive at one year. Ninety percent of patients had grade IV granulocytopenia (very low white blood cells), one died of sepsis, and 30% had grade II or III cardiac dysfunction despite dexrazoxane. The study was stopped early because of excessive toxicity. The authors concluded that high-dose doxorubicin with dexrazoxane was unacceptably toxic in this patient population, while noting that patient numbers were small.

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 clinical trial of a chemotherapy regimen (Cancer and Leukemia Group B study 9631), stopped early
• Who was studied: 10 patients with histologically confirmed malignant mesothelioma (epithelial, sarcomatoid, or mixed) and no prior chemotherapy, enrolled at CALGB institutions in the USA between November 1996 and March 1997. All 10 were eligible. 33 patients had been planned.
• Exposure: Treatment, not asbestos, was studied. Doxorubicin was given every 21 days for up to four cycles, preceded by dexrazoxane and followed by GM-CSF. The first patient received doxorubicin 120 mg/m2 with dexrazoxane 1200 mg/m2. After that patient's toxicity, later patients received doxorubicin 90 mg/m2 with dexrazoxane 900 mg/m2; patient number 2 received the first cycle at the higher dose.
• Main results:
  • No objective tumor responses among the 10 patients.
  • 5 patients had stable disease and 1 progressed. 4 could not be evaluated: 2 because of early death and 2 because they withdrew consent.
  • Median failure-free survival was 2.76 months and median overall survival 4.8 months, with 20% of patients alive at one year.
  • 90% of patients had grade IV granulocytopenia, and one patient died a septic death.
  • Grade IV thrombocytopenia (very low platelets) occurred in 50% of patients.
  • Grade II or III cardiac dysfunction occurred in 30% of patients despite dexrazoxane.
  • Grade II/III anemia occurred in 90% of patients.
  • Grade III/IV fatigue and malaise occurred in 40% of patients.
  • The study was stopped early because of excessive toxicity.
  • Patient characteristics table: asbestos exposure was recorded as yes for 6 patients (60%), no for 1 (10%) and unknown for 3 (30%).
• The authors' conclusion: The authors concluded that high-dose doxorubicin given with dexrazoxane is unacceptably toxic in patients with malignant mesothelioma.
• Limitations the authors state:
  • The authors noted that patient numbers were small.
  • The authors used a lower dexrazoxane-to-doxorubicin ratio (10:1, following FDA recommendations) than in the earlier phase I study (20:1). They stated it is unclear whether this lower dexrazoxane dose contributed to the cardiac toxicity seen.

Topics

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

Medical terms in this study, explained in our Lexicon: Doxorubicin, Malignant Mesothelioma.

Related studies

• A phase II trial of dose-escalated doxorubicin and ifosfamide/mesna in patients with malignant mesothelioma — L.Y. Dirix, J. van Meerbeeck, et al. (1994)
• Phase I combination study of the PARP inhibitor veliparib plus carboplatin and gemcitabine in patients with advanced ovarian cancer and other solid malignancies — H.J. Gray, K. Bell-McGuinn, et al. (2018)
• Trimetrexate in malignant mesothelioma: A Cancer and Leukemia Group B Phase II study — N.J. Vogelzang, L.B. Weissman, et al. (1994)
• Valproate-doxorubicin: promising therapy for progressing mesothelioma. A phase II study — A. Scherpereel, T. Berghmans, et al. (2011)
• Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study — G. Hillerdal, J.B. Sorensen, et al. (2008)
• Phase-II study with the combination of cisplatin and doxorubicin in advanced malignant mesothelioma of the pleura — H. Henss, H.H. Fiebig, et al. (1988)

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