Randomized study of cisplatin dose intensity in poor-risk germ cell tumors: A southeastern cancer study group and southwest oncology group protocol

Craig R. Nichols, Stephen D. Williams, Patrick Loehrer, F. Anthony Greco, E. David Crawford, John Weetlaufer, Michael E. Miller, Albert Bartolucci, Lee Schacter, Lawrence Einhorn

Research output: Contribution to journalArticle

258 Citations (Scopus)

Abstract

Between 1984 and 1989, 159 patients presenting with advanced germ cell cancer were entered on a randomized clinical trial comparing the efficacy and toxicity of etoposide and bleomycin and either standard-dose cisplatin (20 mg/m2 daily for 5 days) or high-dose cisplatin (40 mg/m2 daily for 5 days). Of the 159 patients, 153 were assessable for toxicity and response. As expected, patients receiving the high-dose cisplatin regimen experienced significantly more neurotoxicity, ototoxicity, nausea and vomiting, and myelosuppression. Four patients (3%) died related to therapy. Despite the toxicity encountered, dose intensity was maintained. Overall, 84% of patients in the high-dose arm received 80% or more of the projected dose of cisplatin, etoposide, and bleomycin; and 90% of patients on the standard-dose arm received 80% or more of the projected dose. Of the 76 eligible patients randomized to receive the high-dose cisplatin regimen, 52 (68%) became disease-free with chemotherapy alone or with subsequent resection of residual teratoma or cancer. Of the 77 patients randomized to the standard-dose arm, 56 (73%) became disease-free with chemotherapy alone or with surgery. Median follow-up is now 24 months. Eleven patients (three high-dose and eight standard-dose) relapsed from disease-free status. Overall, 74% of patients receiving the high-dose cisplatin regimen are alive, and 63% are continuously free of disease. Of the patients receiving the standard-dose cisplatin regimen, 74% are alive, and 61 % are continuously free of disease. This randomized prospective trial in advanced germ cell cancer achieved dose intensity of the most active single agent in this disease. This dose intensity did not translate into an improved survival or cure. We conclude that dose escalation of cisplatin beyond standard doses results in excess toxicity with no accompanying therapeutic benefit.

Original languageEnglish (US)
Pages (from-to)1163-1172
Number of pages10
JournalJournal of Clinical Oncology
Volume9
Issue number7
StatePublished - 1991

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Germ Cell and Embryonal Neoplasms
Cisplatin
Neoplasms
Bleomycin
Etoposide
Drug Therapy
Teratoma
Nausea
Vomiting
Randomized Controlled Trials

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Randomized study of cisplatin dose intensity in poor-risk germ cell tumors : A southeastern cancer study group and southwest oncology group protocol. / Nichols, Craig R.; Williams, Stephen D.; Loehrer, Patrick; Anthony Greco, F.; David Crawford, E.; Weetlaufer, John; Miller, Michael E.; Bartolucci, Albert; Schacter, Lee; Einhorn, Lawrence.

In: Journal of Clinical Oncology, Vol. 9, No. 7, 1991, p. 1163-1172.

Research output: Contribution to journalArticle

Nichols, CR, Williams, SD, Loehrer, P, Anthony Greco, F, David Crawford, E, Weetlaufer, J, Miller, ME, Bartolucci, A, Schacter, L & Einhorn, L 1991, 'Randomized study of cisplatin dose intensity in poor-risk germ cell tumors: A southeastern cancer study group and southwest oncology group protocol', Journal of Clinical Oncology, vol. 9, no. 7, pp. 1163-1172.
Nichols, Craig R. ; Williams, Stephen D. ; Loehrer, Patrick ; Anthony Greco, F. ; David Crawford, E. ; Weetlaufer, John ; Miller, Michael E. ; Bartolucci, Albert ; Schacter, Lee ; Einhorn, Lawrence. / Randomized study of cisplatin dose intensity in poor-risk germ cell tumors : A southeastern cancer study group and southwest oncology group protocol. In: Journal of Clinical Oncology. 1991 ; Vol. 9, No. 7. pp. 1163-1172.
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abstract = "Between 1984 and 1989, 159 patients presenting with advanced germ cell cancer were entered on a randomized clinical trial comparing the efficacy and toxicity of etoposide and bleomycin and either standard-dose cisplatin (20 mg/m2 daily for 5 days) or high-dose cisplatin (40 mg/m2 daily for 5 days). Of the 159 patients, 153 were assessable for toxicity and response. As expected, patients receiving the high-dose cisplatin regimen experienced significantly more neurotoxicity, ototoxicity, nausea and vomiting, and myelosuppression. Four patients (3{\%}) died related to therapy. Despite the toxicity encountered, dose intensity was maintained. Overall, 84{\%} of patients in the high-dose arm received 80{\%} or more of the projected dose of cisplatin, etoposide, and bleomycin; and 90{\%} of patients on the standard-dose arm received 80{\%} or more of the projected dose. Of the 76 eligible patients randomized to receive the high-dose cisplatin regimen, 52 (68{\%}) became disease-free with chemotherapy alone or with subsequent resection of residual teratoma or cancer. Of the 77 patients randomized to the standard-dose arm, 56 (73{\%}) became disease-free with chemotherapy alone or with surgery. Median follow-up is now 24 months. Eleven patients (three high-dose and eight standard-dose) relapsed from disease-free status. Overall, 74{\%} of patients receiving the high-dose cisplatin regimen are alive, and 63{\%} are continuously free of disease. Of the patients receiving the standard-dose cisplatin regimen, 74{\%} are alive, and 61 {\%} are continuously free of disease. This randomized prospective trial in advanced germ cell cancer achieved dose intensity of the most active single agent in this disease. This dose intensity did not translate into an improved survival or cure. We conclude that dose escalation of cisplatin beyond standard doses results in excess toxicity with no accompanying therapeutic benefit.",
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AU - Anthony Greco, F.

AU - David Crawford, E.

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AU - Miller, Michael E.

AU - Bartolucci, Albert

AU - Schacter, Lee

AU - Einhorn, Lawrence

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