TY - JOUR
T1 - Phase i clinical trial of temsirolimus and vinorelbine in advanced solid tumors
AU - Piatek, Caroline I.
AU - Raja, Grace L.
AU - Ji, Lingyun
AU - Gitlitz, Barbara Jennifer
AU - Dorff, Tanya B.
AU - Quinn, David I.
AU - Hu, James
AU - El-Khoueiry, Anthony B.
AU - Pham, Huyen Q.
AU - Roman, Lynda
AU - Garcia, Agustin A.
N1 - Publisher Copyright:
© 2014 Springer-Verlag Berlin Heidelberg.
PY - 2014/12
Y1 - 2014/12
N2 - 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.
AB - 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.
KW - Metastatic carcinoma
KW - Phase I trial
KW - Temsirolimus
KW - Vinorelbine
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U2 - 10.1007/s00280-014-2600-z
DO - 10.1007/s00280-014-2600-z
M3 - Article
C2 - 25374407
AN - SCOPUS:84922072911
SN - 0344-5704
VL - 74
SP - 1227
EP - 1234
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 6
ER -