Faculty Collaboration Database

A phase I trial of gemcitabine in combination with patupilone in patients with advanced solid tumors. Cancer Chemother Pharmacol 2008 Sep;62(4):727-33

Date

01/04/2008

Pubmed ID

18172649

DOI

10.1007/s00280-007-0656-8

Scopus ID

2-s2.0-47549111409 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

INTRODUCTION: Chemotherapy regimens including gemcitabine in combination with microtubule inhibitors such as docetaxel and paclitaxel have wide clinical application. Patupilone is a novel tubulin-polymerizing agent with activity against paclitaxel-resistant cell lines. We conducted a phase I trial to assess the maximum tolerated dose, dose limiting toxicity (DLT) and antitumor activity of gemcitabine and patupilone.

METHODS: Patients with refractory solid tumors enrolled in cohorts of three. Cohorts received fixed doses of gemcitabine (1,000 or 750 mg/m(2)) along with escalating doses of patupilone (1.5-3 mg/m(2)) on days 1 and 8 of a 21-day cycle.

RESULTS: Twenty-seven patients received a total of 99 courses of treatment on study. Hematologic toxicity in the first cohort required a modification of the protocol to decrease the gemcitabine dose. Subsequent patients received gemcitabine 750 mg/m(2) and escalating doses of patupilone from 1.5 to 3 mg/m(2). DLTs were grade 3 asthenia and grade 3 dehydration. There was also one treatment-related death due to neutropenic infection. Other clinically significant toxicities were persistent asthenia and persistent nausea. Four patients, one each with pancreatic cancer, esophageal carcinoma, cholangiocarcinoma and gallbladder carcinoma, experienced a partial response.

CONCLUSIONS: The dose-limiting toxicities of gemcitabine and patupilone were asthenia and dehydration. Dose reductions also occurred due to persistent fatigue that was not dose-limiting. However, patients with advanced malignancies were able to tolerate gemcitabine and patupilone at doses that resulted in clinical benefit. The recommended phase II dose for this schedule is gemcitabine 750 mg/m(2) and patupilone 1.5 mg/m(2) on days 1 and 8 of a 21-day cycle.

Author List

Schelman W, Morgan-Meadows S, Bailey H, Holen K, Thomas JP, Eickhoff J, Brandon H, Oliver K, Alberti D, Wilding G

Author

James P. Thomas MD, PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Deoxycytidine
Dose-Response Relationship, Drug
Epothilones
Female
Humans
Male
Maximum Tolerated Dose
Middle Aged
Neoplasms
Treatment Outcome