Phase I clinical trial of temsirolimus and vinorelbine in advanced solid tumors.
OBJECTIVE
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/m(2) given days 1 and 15 every 4 weeks was found to be the MTD. This dose combination is considered feasible in phase II trials.
Division of Medical Oncology, Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Caroline I
CI
Piatek
Grace L
GL
Raja
Lingyun
L
Ji
Barbara Jennifer
BJ
Gitlitz
Tanya B
TB
Dorff
David I
DI
Quinn
James
J
Hu
Anthony B
AB
El-Khoueiry
Huyen Q
HQ
Pham
Lynda
L
Roman
Agustin A
AA
Garcia
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
D014747:Vinblastine; C401859:temsirolimus; D000077235:Vinorelbine; D020123:Sirolimus