Paclitaxel poliglumex and carboplatin as first-line therapy in ovarian, peritoneal or fallopian tube cancer: A phase I and feasibility trial of the Gynecologic Oncology Group

Mark A. Morgan, Kathleen M. Darcy, Peter G. Rose, Koenraad De Geest, Michael A. Bookman, James K. Aikins, Michael W. Sill, Robert S. Mannel, Cecilia Allievi, Merrill J. Egorin

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Abstract

Purpose: To estimate the maximum tolerated dose (MTD) of paclitaxel poliglumex (PPX) in combination with carboplatin in patients with chemotherapy-naive ovarian, primary peritoneal or fallopian tube cancer, and to assess the feasibility of administering multiple cycles of this regimen. Methods: The first 11 patients were treated in a standard 3 + 3 dose-seeking design, with carboplatin held constant at area under the curve (AUC) of 6 and PPX at 225, 175 or 135 mg/m2. Pharmacokinetics of PPX and carboplatin were evaluated during this dose-seeking component of the trial. MTD was defined by acute dose-limiting toxicities (DLT) in the first cycle. Twenty additional evaluable patients were treated at the estimated MTD to assess the feasibility of this regimen over ≥ 4cycles. Results: PPX at 225 mg/m2 resulted in DLT in 2/3 patients, and was de-escalated first to 175 mg/m2 and then to 135 mg/m2. PPX slowly hydrolyzed to paclitaxel and did not alter the pharmacokinetics of carboplatin. DLT within the first 4-cycles were observed in 3 patients (15%) treated at the MTD: neutropenia > 2weeks (2), febrile neutropenia (1). Nineteen patients (95%) experienced grade 4 neutropenia. Sixteen patients (80%) had at least one episode of grade 3 thrombocytopenia. Three patients (15%) had grade 2 and one had grade 3 peripheral neuropathy. Complete response by CA-125 was 75%. Conclusions: The recommended dose of PPX of 135 mg/m2 with carboplatin (AUC = 6) in newly diagnosed ovarian cancer was feasible for multiple cycles, but hematologic toxicity was greater compared with standard carboplatin and 3-hour paclitaxel.

Original languageEnglish (US)
Pages (from-to)329-335
Number of pages7
JournalGynecologic Oncology
Volume110
Issue number3
DOIs
StatePublished - Sep 2008
Externally publishedYes

Fingerprint

Fallopian Tube Neoplasms
Carboplatin
Maximum Tolerated Dose
Therapeutics
Paclitaxel
Neutropenia
Area Under Curve
Pharmacokinetics
Febrile Neutropenia
paclitaxel poliglumex
Peripheral Nervous System Diseases
Ovarian Neoplasms
Drug Therapy

Keywords

  • Carboplatin
  • Chemotherapy
  • Ovarian cancer
  • Paclitaxel poliglumex
  • Phase I trial

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Paclitaxel poliglumex and carboplatin as first-line therapy in ovarian, peritoneal or fallopian tube cancer : A phase I and feasibility trial of the Gynecologic Oncology Group. / Morgan, Mark A.; Darcy, Kathleen M.; Rose, Peter G.; De Geest, Koenraad; Bookman, Michael A.; Aikins, James K.; Sill, Michael W.; Mannel, Robert S.; Allievi, Cecilia; Egorin, Merrill J.

In: Gynecologic Oncology, Vol. 110, No. 3, 09.2008, p. 329-335.

Research output: Contribution to journalArticle

Morgan, Mark A. ; Darcy, Kathleen M. ; Rose, Peter G. ; De Geest, Koenraad ; Bookman, Michael A. ; Aikins, James K. ; Sill, Michael W. ; Mannel, Robert S. ; Allievi, Cecilia ; Egorin, Merrill J. / Paclitaxel poliglumex and carboplatin as first-line therapy in ovarian, peritoneal or fallopian tube cancer : A phase I and feasibility trial of the Gynecologic Oncology Group. In: Gynecologic Oncology. 2008 ; Vol. 110, No. 3. pp. 329-335.
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abstract = "Purpose: To estimate the maximum tolerated dose (MTD) of paclitaxel poliglumex (PPX) in combination with carboplatin in patients with chemotherapy-naive ovarian, primary peritoneal or fallopian tube cancer, and to assess the feasibility of administering multiple cycles of this regimen. Methods: The first 11 patients were treated in a standard 3 + 3 dose-seeking design, with carboplatin held constant at area under the curve (AUC) of 6 and PPX at 225, 175 or 135 mg/m2. Pharmacokinetics of PPX and carboplatin were evaluated during this dose-seeking component of the trial. MTD was defined by acute dose-limiting toxicities (DLT) in the first cycle. Twenty additional evaluable patients were treated at the estimated MTD to assess the feasibility of this regimen over ≥ 4cycles. Results: PPX at 225 mg/m2 resulted in DLT in 2/3 patients, and was de-escalated first to 175 mg/m2 and then to 135 mg/m2. PPX slowly hydrolyzed to paclitaxel and did not alter the pharmacokinetics of carboplatin. DLT within the first 4-cycles were observed in 3 patients (15{\%}) treated at the MTD: neutropenia > 2weeks (2), febrile neutropenia (1). Nineteen patients (95{\%}) experienced grade 4 neutropenia. Sixteen patients (80{\%}) had at least one episode of grade 3 thrombocytopenia. Three patients (15{\%}) had grade 2 and one had grade 3 peripheral neuropathy. Complete response by CA-125 was 75{\%}. Conclusions: The recommended dose of PPX of 135 mg/m2 with carboplatin (AUC = 6) in newly diagnosed ovarian cancer was feasible for multiple cycles, but hematologic toxicity was greater compared with standard carboplatin and 3-hour paclitaxel.",
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T1 - Paclitaxel poliglumex and carboplatin as first-line therapy in ovarian, peritoneal or fallopian tube cancer

T2 - A phase I and feasibility trial of the Gynecologic Oncology Group

AU - Morgan, Mark A.

AU - Darcy, Kathleen M.

AU - Rose, Peter G.

AU - De Geest, Koenraad

AU - Bookman, Michael A.

AU - Aikins, James K.

AU - Sill, Michael W.

AU - Mannel, Robert S.

AU - Allievi, Cecilia

AU - Egorin, Merrill J.

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N2 - Purpose: To estimate the maximum tolerated dose (MTD) of paclitaxel poliglumex (PPX) in combination with carboplatin in patients with chemotherapy-naive ovarian, primary peritoneal or fallopian tube cancer, and to assess the feasibility of administering multiple cycles of this regimen. Methods: The first 11 patients were treated in a standard 3 + 3 dose-seeking design, with carboplatin held constant at area under the curve (AUC) of 6 and PPX at 225, 175 or 135 mg/m2. Pharmacokinetics of PPX and carboplatin were evaluated during this dose-seeking component of the trial. MTD was defined by acute dose-limiting toxicities (DLT) in the first cycle. Twenty additional evaluable patients were treated at the estimated MTD to assess the feasibility of this regimen over ≥ 4cycles. Results: PPX at 225 mg/m2 resulted in DLT in 2/3 patients, and was de-escalated first to 175 mg/m2 and then to 135 mg/m2. PPX slowly hydrolyzed to paclitaxel and did not alter the pharmacokinetics of carboplatin. DLT within the first 4-cycles were observed in 3 patients (15%) treated at the MTD: neutropenia > 2weeks (2), febrile neutropenia (1). Nineteen patients (95%) experienced grade 4 neutropenia. Sixteen patients (80%) had at least one episode of grade 3 thrombocytopenia. Three patients (15%) had grade 2 and one had grade 3 peripheral neuropathy. Complete response by CA-125 was 75%. Conclusions: The recommended dose of PPX of 135 mg/m2 with carboplatin (AUC = 6) in newly diagnosed ovarian cancer was feasible for multiple cycles, but hematologic toxicity was greater compared with standard carboplatin and 3-hour paclitaxel.

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KW - Phase I trial

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