A phase I study of paclitaxel, doxorubicin, and cisplatin in patients with previously untreated epithelial ovarian cancer

R. Wendel Naumann, Ronald D. Alvarez, George A. Omura, Ellen Segars, Larry Kilgore, Edward E. Partridge

Research output: Contribution to journalArticle

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Abstract

Objective. Although doxorubicin is not currently popular as a primary agent in ovarian cancer, overviews of previous studies suggest that the inclusion of doxorubicin may have improved outcome. The purpose of this phase I study was to determine the maximal dose of doxorubicin that could be added to standard doses of paclitaxel and cisplatin with G-CSF support. Methods. Women with FIGO stage III or IV epithelial ovarian cancer were primarily treated with escalating doses of doxorubicin in combination with paclitaxel (135 mg/m2 over 24 h) and cisplatin (75 mg/m2) every 3 weeks. Doxorubicin was started at 30 mg/m2 and escalated by 10 mg/m2 per treatment level. All patients received G-CSF support. Results. Eleven patients were treated at two dose levels. Dose limiting toxicity (DLT) was reached at the 40 mg/m2 dose of doxorubicin. All patients experienced grade 4 neutropenia although none required hospitalization. DLT included renal toxicity and prolonged thrombocytopenia. Despite vigorous antiemetic regimens 60% of patients experienced severe nausea and vomiting. Nine patients were assessable for response. Eight patients have had a complete clinical response (89%). Of the five patients undergoing second-look laparotomy two were negative. Conclusions. The maximum tolerated dose of doxorubicin in this three-drug regimen is 30 mg/m2 with standard doses of paclitaxel and cisplatin. Hematologic toxicity is manageable using G-CSF. Doxorubicin appears to increase the renal toxicity of cisplatin which may be exaggerated by marked nausea and vomiting. This is an active but toxic regimen and alternative sequences and strategies should be evaluated.

Original languageEnglish (US)
Pages (from-to)450-453
Number of pages4
JournalGynecologic oncology
Volume71
Issue number3
DOIs
StatePublished - Jan 1 1998

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Doxorubicin
Granulocyte Colony-Stimulating Factor
Nausea
Cisplatin
Vomiting
Kidney
Antiemetics
Maximum Tolerated Dose
TP protocol
Ovarian epithelial cancer
Poisons
Paclitaxel
Neutropenia
Thrombocytopenia
Ovarian Neoplasms
Laparotomy
Hospitalization
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynecology

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A phase I study of paclitaxel, doxorubicin, and cisplatin in patients with previously untreated epithelial ovarian cancer. / Naumann, R. Wendel; Alvarez, Ronald D.; Omura, George A.; Segars, Ellen; Kilgore, Larry; Partridge, Edward E.

In: Gynecologic oncology, Vol. 71, No. 3, 01.01.1998, p. 450-453.

Research output: Contribution to journalArticle

Naumann, R. Wendel ; Alvarez, Ronald D. ; Omura, George A. ; Segars, Ellen ; Kilgore, Larry ; Partridge, Edward E. / A phase I study of paclitaxel, doxorubicin, and cisplatin in patients with previously untreated epithelial ovarian cancer. In: Gynecologic oncology. 1998 ; Vol. 71, No. 3. pp. 450-453.
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N2 - Objective. Although doxorubicin is not currently popular as a primary agent in ovarian cancer, overviews of previous studies suggest that the inclusion of doxorubicin may have improved outcome. The purpose of this phase I study was to determine the maximal dose of doxorubicin that could be added to standard doses of paclitaxel and cisplatin with G-CSF support. Methods. Women with FIGO stage III or IV epithelial ovarian cancer were primarily treated with escalating doses of doxorubicin in combination with paclitaxel (135 mg/m2 over 24 h) and cisplatin (75 mg/m2) every 3 weeks. Doxorubicin was started at 30 mg/m2 and escalated by 10 mg/m2 per treatment level. All patients received G-CSF support. Results. Eleven patients were treated at two dose levels. Dose limiting toxicity (DLT) was reached at the 40 mg/m2 dose of doxorubicin. All patients experienced grade 4 neutropenia although none required hospitalization. DLT included renal toxicity and prolonged thrombocytopenia. Despite vigorous antiemetic regimens 60% of patients experienced severe nausea and vomiting. Nine patients were assessable for response. Eight patients have had a complete clinical response (89%). Of the five patients undergoing second-look laparotomy two were negative. Conclusions. The maximum tolerated dose of doxorubicin in this three-drug regimen is 30 mg/m2 with standard doses of paclitaxel and cisplatin. Hematologic toxicity is manageable using G-CSF. Doxorubicin appears to increase the renal toxicity of cisplatin which may be exaggerated by marked nausea and vomiting. This is an active but toxic regimen and alternative sequences and strategies should be evaluated.

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