Dose-intensive chemotherapy in refractory germ cell cancer - A phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation

C. R. Nichols, G. Tricot, S. D. Williams, K. Van Besien, Patrick Loehrer, B. J. Roth, L. Akard, R. Hoffman, R. Goulet, S. N. Wolff, L. Giannone, J. Greer, Lawrence Einhorn, J. Jansen

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Abstract

Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or bearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistent to conventional-dose cisplatin-based therapies.

Original languageEnglish
Pages (from-to)932-939
Number of pages8
JournalJournal of Clinical Oncology
Volume7
Issue number7
StatePublished - 1989

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Autologous Transplantation
Germ Cell and Embryonal Neoplasms
Carboplatin
Etoposide
Bone Marrow Transplantation
Cisplatin
Drug Therapy
Enterocolitis
Therapeutics
Ifosfamide
Granulocytes
Sepsis
Fever
Bone Marrow

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Dose-intensive chemotherapy in refractory germ cell cancer - A phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation. / Nichols, C. R.; Tricot, G.; Williams, S. D.; Van Besien, K.; Loehrer, Patrick; Roth, B. J.; Akard, L.; Hoffman, R.; Goulet, R.; Wolff, S. N.; Giannone, L.; Greer, J.; Einhorn, Lawrence; Jansen, J.

In: Journal of Clinical Oncology, Vol. 7, No. 7, 1989, p. 932-939.

Research output: Contribution to journalArticle

Nichols, CR, Tricot, G, Williams, SD, Van Besien, K, Loehrer, P, Roth, BJ, Akard, L, Hoffman, R, Goulet, R, Wolff, SN, Giannone, L, Greer, J, Einhorn, L & Jansen, J 1989, 'Dose-intensive chemotherapy in refractory germ cell cancer - A phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation', Journal of Clinical Oncology, vol. 7, no. 7, pp. 932-939.
Nichols, C. R. ; Tricot, G. ; Williams, S. D. ; Van Besien, K. ; Loehrer, Patrick ; Roth, B. J. ; Akard, L. ; Hoffman, R. ; Goulet, R. ; Wolff, S. N. ; Giannone, L. ; Greer, J. ; Einhorn, Lawrence ; Jansen, J. / Dose-intensive chemotherapy in refractory germ cell cancer - A phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation. In: Journal of Clinical Oncology. 1989 ; Vol. 7, No. 7. pp. 932-939.
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abstract = "Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67{\%}) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35{\%}) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or bearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21{\%}) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44{\%}) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistent to conventional-dose cisplatin-based therapies.",
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T1 - Dose-intensive chemotherapy in refractory germ cell cancer - A phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation

AU - Nichols, C. R.

AU - Tricot, G.

AU - Williams, S. D.

AU - Van Besien, K.

AU - Loehrer, Patrick

AU - Roth, B. J.

AU - Akard, L.

AU - Hoffman, R.

AU - Goulet, R.

AU - Wolff, S. N.

AU - Giannone, L.

AU - Greer, J.

AU - Einhorn, Lawrence

AU - Jansen, J.

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N2 - Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or bearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistent to conventional-dose cisplatin-based therapies.

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