Dihydro-5-azacytidine and cisplatin in the treatment of malignant mesothelioma: A Phase II study by the Cancer and Leukemia Group B

Brian L. Samuels, James E. Herndon, David C. Harmon, Robert Carey, Joseph Aisner, Joseph M. Corson, Yasunosuke Suzuki, Mark R. Green, Nicholas J. Vogelzang

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

BACKGROUND. In a prior Cancer and Leukemia Group B (CALGB) Phase II trial of patients with advanced, previously untreated mesothelioma, dihydro- 5-azacytidine (DHAC) demonstrated a 17% response rate, including 1 complete response, with only mild myelosuppression. This Phase II study (CALGB 9031) was conducted to determine the effectiveness of and toxicities that would result from adding cisplatin to DHAC administered to the same patient population. METHODS. Thirty-six patients were treated with concurrent DHAC at 1500 mg/m2/day for 5 days by continuous infusion and cisplatin 15 mg/m2 daily for 5 days. Therapy was repeated every 3 weeks. Cisplatin was to be increased to 20 mg/m2 daily in subsequent cycles if toxicity was minimal. Therapy was continued until disease progression or excessive toxicity mandated discontinuation. RESULTS. Overall, 5 objective responses were observed in 29 evaluated patients (objective response rate, 17%). The median duration of response was 6.6 months. Median survival was 6.4 months, with a median time to clinical failure of 2.7 months. The major toxicity noted was significant chest/pericardial pain, as was observed with DHAC alone. There were 2 early deaths of unknown cause on Days 9 and 17 of therapy, respectively. Significant leukopenia was observed in 29% of patients, but there were no neutropenic fevers. CONCLUSIONS. The addition of cisplatin to DHAC did not increase the response rate over that observed with DHAC alone in patients with mesothelioma; however, it did increase toxicity, especially leukopenia. This combination is not recommended for further studies involving mesothelioma patients.

Original languageEnglish (US)
Pages (from-to)1578-1584
Number of pages7
JournalCancer
Volume82
Issue number8
DOIs
StatePublished - Apr 15 1998

Fingerprint

5,6-dihydro-5-azacytidine
Cisplatin
Leukemia
Mesothelioma
Neoplasms
Leukopenia
Therapeutics
Malignant Mesothelioma
Chest Pain
Disease Progression
Cause of Death
Fever

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Cisplatin
  • Dihydro-5-azacytidine
  • Medical oncology
  • Mesothelioma
  • Phase II study

Cite this

Samuels, Brian L. ; Herndon, James E. ; Harmon, David C. ; Carey, Robert ; Aisner, Joseph ; Corson, Joseph M. ; Suzuki, Yasunosuke ; Green, Mark R. ; Vogelzang, Nicholas J. / Dihydro-5-azacytidine and cisplatin in the treatment of malignant mesothelioma : A Phase II study by the Cancer and Leukemia Group B. In: Cancer. 1998 ; Vol. 82, No. 8. pp. 1578-1584.
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title = "Dihydro-5-azacytidine and cisplatin in the treatment of malignant mesothelioma: A Phase II study by the Cancer and Leukemia Group B",
abstract = "BACKGROUND. In a prior Cancer and Leukemia Group B (CALGB) Phase II trial of patients with advanced, previously untreated mesothelioma, dihydro- 5-azacytidine (DHAC) demonstrated a 17{\%} response rate, including 1 complete response, with only mild myelosuppression. This Phase II study (CALGB 9031) was conducted to determine the effectiveness of and toxicities that would result from adding cisplatin to DHAC administered to the same patient population. METHODS. Thirty-six patients were treated with concurrent DHAC at 1500 mg/m2/day for 5 days by continuous infusion and cisplatin 15 mg/m2 daily for 5 days. Therapy was repeated every 3 weeks. Cisplatin was to be increased to 20 mg/m2 daily in subsequent cycles if toxicity was minimal. Therapy was continued until disease progression or excessive toxicity mandated discontinuation. RESULTS. Overall, 5 objective responses were observed in 29 evaluated patients (objective response rate, 17{\%}). The median duration of response was 6.6 months. Median survival was 6.4 months, with a median time to clinical failure of 2.7 months. The major toxicity noted was significant chest/pericardial pain, as was observed with DHAC alone. There were 2 early deaths of unknown cause on Days 9 and 17 of therapy, respectively. Significant leukopenia was observed in 29{\%} of patients, but there were no neutropenic fevers. CONCLUSIONS. The addition of cisplatin to DHAC did not increase the response rate over that observed with DHAC alone in patients with mesothelioma; however, it did increase toxicity, especially leukopenia. This combination is not recommended for further studies involving mesothelioma patients.",
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Dihydro-5-azacytidine and cisplatin in the treatment of malignant mesothelioma : A Phase II study by the Cancer and Leukemia Group B. / Samuels, Brian L.; Herndon, James E.; Harmon, David C.; Carey, Robert; Aisner, Joseph; Corson, Joseph M.; Suzuki, Yasunosuke; Green, Mark R.; Vogelzang, Nicholas J.

In: Cancer, Vol. 82, No. 8, 15.04.1998, p. 1578-1584.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dihydro-5-azacytidine and cisplatin in the treatment of malignant mesothelioma

T2 - A Phase II study by the Cancer and Leukemia Group B

AU - Samuels, Brian L.

AU - Herndon, James E.

AU - Harmon, David C.

AU - Carey, Robert

AU - Aisner, Joseph

AU - Corson, Joseph M.

AU - Suzuki, Yasunosuke

AU - Green, Mark R.

AU - Vogelzang, Nicholas J.

PY - 1998/4/15

Y1 - 1998/4/15

N2 - BACKGROUND. In a prior Cancer and Leukemia Group B (CALGB) Phase II trial of patients with advanced, previously untreated mesothelioma, dihydro- 5-azacytidine (DHAC) demonstrated a 17% response rate, including 1 complete response, with only mild myelosuppression. This Phase II study (CALGB 9031) was conducted to determine the effectiveness of and toxicities that would result from adding cisplatin to DHAC administered to the same patient population. METHODS. Thirty-six patients were treated with concurrent DHAC at 1500 mg/m2/day for 5 days by continuous infusion and cisplatin 15 mg/m2 daily for 5 days. Therapy was repeated every 3 weeks. Cisplatin was to be increased to 20 mg/m2 daily in subsequent cycles if toxicity was minimal. Therapy was continued until disease progression or excessive toxicity mandated discontinuation. RESULTS. Overall, 5 objective responses were observed in 29 evaluated patients (objective response rate, 17%). The median duration of response was 6.6 months. Median survival was 6.4 months, with a median time to clinical failure of 2.7 months. The major toxicity noted was significant chest/pericardial pain, as was observed with DHAC alone. There were 2 early deaths of unknown cause on Days 9 and 17 of therapy, respectively. Significant leukopenia was observed in 29% of patients, but there were no neutropenic fevers. CONCLUSIONS. The addition of cisplatin to DHAC did not increase the response rate over that observed with DHAC alone in patients with mesothelioma; however, it did increase toxicity, especially leukopenia. This combination is not recommended for further studies involving mesothelioma patients.

AB - BACKGROUND. In a prior Cancer and Leukemia Group B (CALGB) Phase II trial of patients with advanced, previously untreated mesothelioma, dihydro- 5-azacytidine (DHAC) demonstrated a 17% response rate, including 1 complete response, with only mild myelosuppression. This Phase II study (CALGB 9031) was conducted to determine the effectiveness of and toxicities that would result from adding cisplatin to DHAC administered to the same patient population. METHODS. Thirty-six patients were treated with concurrent DHAC at 1500 mg/m2/day for 5 days by continuous infusion and cisplatin 15 mg/m2 daily for 5 days. Therapy was repeated every 3 weeks. Cisplatin was to be increased to 20 mg/m2 daily in subsequent cycles if toxicity was minimal. Therapy was continued until disease progression or excessive toxicity mandated discontinuation. RESULTS. Overall, 5 objective responses were observed in 29 evaluated patients (objective response rate, 17%). The median duration of response was 6.6 months. Median survival was 6.4 months, with a median time to clinical failure of 2.7 months. The major toxicity noted was significant chest/pericardial pain, as was observed with DHAC alone. There were 2 early deaths of unknown cause on Days 9 and 17 of therapy, respectively. Significant leukopenia was observed in 29% of patients, but there were no neutropenic fevers. CONCLUSIONS. The addition of cisplatin to DHAC did not increase the response rate over that observed with DHAC alone in patients with mesothelioma; however, it did increase toxicity, especially leukopenia. This combination is not recommended for further studies involving mesothelioma patients.

KW - Cisplatin

KW - Dihydro-5-azacytidine

KW - Medical oncology

KW - Mesothelioma

KW - Phase II study

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