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Phase I clinical trial of temsirolimus and vinorelbine in advanced solid tumors

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Abstract

Purpose

To determine the maximal tolerated dose (MTD) of the combination of weekly temsirolimus and every other week vinorelbine in patients with advanced or refractory solid tumors.

Methods

Patients were treated with intravenous temsirolimus on days 1, 8, 15, and 22 and intravenous vinorelbine on days 1 and 15. Cycles were repeated every 28 days.

Results

Nineteen patients were enrolled in the study. Tumor types included lung (5), prostate (2), neuroendocrine of pancreas (1), bladder (2), uterus (3), cervix (4), and vagina (2). All patients had received prior chemotherapy. Four patients were enrolled to dose level I, nine to dose level II, and six to dose level III. Six patients were inevaluable and replaced. Fifty-seven total cycles were administered. There was 1 dose-limiting toxicity at level II (grade 3 anorexia/dehydration) and 2 at level III (grade 3 hypokalemia; grade 4 neutropenia). Two patients died at dose level III; one was study-related with grade 4 neutropenia. Grade 3/4 toxicities observed during the first cycle included neutropenia (2), anemia (1), anorexia (1), dehydration (1), hyperglycemia (1), hypertriglyceridemia (1), and hypokalemia (1). Best response included two patients (prostate and non-small cell lung cancer) with partial response and eight patients with stable disease with median duration of best response of 3.2 months.

Conclusions

Temsirolimus 25 mg given days 1, 8, 15, and 22 in combination with vinorelbine 20 mg/m2 given days 1 and 15 every 4 weeks was found to be the MTD. This dose combination is considered feasible in phase II trials.

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Acknowledgments

This study was supported by Pfizer.

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Authors and Affiliations

  1. Division of Medical Oncology, Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

    Caroline I. Piatek, Grace L. Raja, Barbara Jennifer Gitlitz, Tanya B. Dorff, David I. Quinn, James Hu, Anthony B. El-Khoueiry & Agustin A. Garcia

  2. Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

    Lingyun Ji

  3. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

    Huyen Q. Pham & Lynda Roman

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  1. Caroline I. Piatek
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  2. Grace L. Raja
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  3. Lingyun Ji
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  9. Huyen Q. Pham
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  11. Agustin A. Garcia
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Correspondence to Agustin A. Garcia.

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Piatek, C.I., Raja, G.L., Ji, L. et al. Phase I clinical trial of temsirolimus and vinorelbine in advanced solid tumors. Cancer Chemother Pharmacol 74, 1227–1234 (2014). https://doi.org/10.1007/s00280-014-2600-z

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  • DOI: https://doi.org/10.1007/s00280-014-2600-z

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