A phase I study of temsirolimus plus carboplatin plus paclitaxel for patients with recurrent or metastatic (R/M) head and neck squamous cell cancer (HNSCC).
OBJECTIVE
The mammalian target of rapamycin complex 1 (mTORC1) is aberrantly activated in many head and neck squamous cell carcinomas (HNSCCs). This phase I study combines the mTORC1 inhibitor temsirolimus with carboplatin and paclitaxel.


METHODS
This was a single institution phase I study for patients with R/M HNSCC with a standard 3 + 3 design. Three doses of temsirolimus were planned: 15, 20, and 25 mg. Due to excessive toxicity with the original study regimen, the protocol was amended to carboplatin AUC 1.5, paclitaxel 80 mg/m(2), and temsirolimus (according to dose escalation plan), all on days 1 and 8 of a 21-day cycle.


RESULTS
18 patients (14 male, 4 female) enrolled, with median age 56 years (range 33-78). The most common toxicities were anemia, leukopenia, thrombocytopenia, and hyperglycemia. Among all patients treated, the confirmed objective partial response (cPR) rate was 22 %. DLT was not exceeded among 6 patients treated at dose level 3 of the revised protocol, and 4 of 6 subjects treated at this dose level had cPRs.


CONCLUSIONS
The phase II recommended regimen is temsirolimus 25 mg, carboplatin AUC 1.5, and paclitaxel 80 mg/m(2), all on days 1 and 8 of a 21-day cycle. A phase II study of this regimen in R/M HNSCC is ongoing.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 532, New York, NY 10021, USA. furym@mskcc.org
Matthew G
MG
Fury
Eric
E
Sherman
Alan
A
Ho
Nora
N
Katabi
Camelia
C
Sima
Katherine W
KW
Kelly
Oby
O
Nwankwo
Sofia
S
Haque
David G
DG
Pfister
D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
C401859:temsirolimus; D016190:Carboplatin; D017239:Paclitaxel; D020123:Sirolimus