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) Journal Article
| Authors: | Fury, M. G.; Sherman, E.; Ho, A.; Katabi, N.; Sima, C.; Kelly, K. W.; Nwankwo, O.; Haque, S.; Pfister, D. G. |
| Article Title: | 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) |
| Abstract: | Purpose: 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. Conclusion: 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. © 2012 Springer-Verlag. |
| Keywords: | adult; cancer survival; clinical article; controlled study; treatment outcome; aged; middle aged; overall survival; fatigue; neutropenia; carcinoma, squamous cell; cancer combination chemotherapy; cancer growth; diarrhea; dose response; drug efficacy; drug safety; side effect; paclitaxel; outcome assessment; recurrent cancer; carboplatin; low drug dose; multiple cycle treatment; neoplasm recurrence, local; anemia; bone marrow suppression; leukopenia; mucosa inflammation; nausea; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; drug administration schedule; dose-response relationship, drug; temsirolimus; drug dose escalation; hyperglycemia; lymphocytopenia; dysphagia; hyponatremia; head and neck neoplasms; neoplasm metastasis; nausea and vomiting; phase 1 clinical trial; head and neck; sirolimus; phase i; head and neck squamous cell carcinoma; squamous; maintenance chemotherapy |
| Journal Title: | Cancer Chemotherapy and Pharmacology |
| Volume: | 70 |
| Issue: | 1 |
| ISSN: | 0344-5704 |
| Publisher: | Springer |
| Date Published: | 2012-07-01 |
| Start Page: | 121 |
| End Page: | 128 |
| Language: | English |
| DOI: | 10.1007/s00280-012-1894-y |
| PROVIDER: | scopus |
| PUBMED: | 22644799 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2012" - "CODEN: CCPHD" - "Source: Scopus" |
