Phase I study of paclitaxel given by seven-week continuous infusion concurrent with radiation therapy for locally advanced squamous cell carcinoma of the head and neck

D. I. Rosenthal, J. H. Lee, R. Sinard, D. A. Yardley, M. Machtay, D. M. Rosen, M. J. Egorin, R. S. Weber, G. S. Weinstein, A. A. Chalian, L. K. Miller, E. P. Frenkel, D. P. Carbone

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Purpose: Paclitaxel is one of the most active agents for squamous cell carcinoma of the head and neck (SCCHN) and an in vitro radiosensitizer. The dose-response relationship for paclitaxel may depend more on exposure duration than on peak concentration. This National Cancer Institute-sponsored phase I trial was designed to determine the feasibility of combining continuous-infusion (CI) paclitaxel with concurrent radiation therapy (RT). Patients and Methods: Patients with previously untreated stage IVA/B SCCHN were eligible. Primary end points were determination of the maximum-tolerated dose, dose-limiting toxicity, and pharmacokinetics for paclitaxel given by CI (24 hours a day, 7 days a week for 7 weeks) during RT (70 Gy/7 weeks). Results: Twenty-seven patients were enrolled and assessable for toxicity. Nineteen of the patients who completed ≥ 70 Gy were assessable for response. Grade 3 skin and mucosal acute reactions occurred at 10.5 mg/m2/d, but uninterrupted treatment was possible in five of six patients. At 17 mg/m2/d, skin toxicity required a 2-week treatment break for all three patients. The mean paclitaxel serum concentration at dose levels ≥ 6.5 mg/m2/d exceeded that reported to achieve in vitro radiosensitization. Initial locoregional control was achieved in 14 (58%) of 24 of patients treated to 70 Gy, and control persisted in nine (38%). Conclusion: CI paclitaxel with concurrent RT is a feasible and tolerable regimen for patients with advanced SCCHN and good performance status. Preliminary response and survival data are encouraging and suggest that further study is indicated. The recommended phase II dose of paclitaxel by CI is 10.5 mg/m2/d with RT for SCCHN.

Original languageEnglish (US)
Pages (from-to)1363-1373
Number of pages11
JournalJournal of Clinical Oncology
Volume19
Issue number5
StatePublished - Mar 1 2001

Fingerprint

Paclitaxel
Radiotherapy
Endpoint Determination
Skin
Maximum Tolerated Dose
National Cancer Institute (U.S.)
Carcinoma, squamous cell of head and neck
Pharmacokinetics
Survival
Therapeutics
Serum

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rosenthal, D. I., Lee, J. H., Sinard, R., Yardley, D. A., Machtay, M., Rosen, D. M., ... Carbone, D. P. (2001). Phase I study of paclitaxel given by seven-week continuous infusion concurrent with radiation therapy for locally advanced squamous cell carcinoma of the head and neck. Journal of Clinical Oncology, 19(5), 1363-1373.

Phase I study of paclitaxel given by seven-week continuous infusion concurrent with radiation therapy for locally advanced squamous cell carcinoma of the head and neck. / Rosenthal, D. I.; Lee, J. H.; Sinard, R.; Yardley, D. A.; Machtay, M.; Rosen, D. M.; Egorin, M. J.; Weber, R. S.; Weinstein, G. S.; Chalian, A. A.; Miller, L. K.; Frenkel, E. P.; Carbone, D. P.

In: Journal of Clinical Oncology, Vol. 19, No. 5, 01.03.2001, p. 1363-1373.

Research output: Contribution to journalArticle

Rosenthal, DI, Lee, JH, Sinard, R, Yardley, DA, Machtay, M, Rosen, DM, Egorin, MJ, Weber, RS, Weinstein, GS, Chalian, AA, Miller, LK, Frenkel, EP & Carbone, DP 2001, 'Phase I study of paclitaxel given by seven-week continuous infusion concurrent with radiation therapy for locally advanced squamous cell carcinoma of the head and neck', Journal of Clinical Oncology, vol. 19, no. 5, pp. 1363-1373.
Rosenthal, D. I. ; Lee, J. H. ; Sinard, R. ; Yardley, D. A. ; Machtay, M. ; Rosen, D. M. ; Egorin, M. J. ; Weber, R. S. ; Weinstein, G. S. ; Chalian, A. A. ; Miller, L. K. ; Frenkel, E. P. ; Carbone, D. P. / Phase I study of paclitaxel given by seven-week continuous infusion concurrent with radiation therapy for locally advanced squamous cell carcinoma of the head and neck. In: Journal of Clinical Oncology. 2001 ; Vol. 19, No. 5. pp. 1363-1373.
@article{0c90cfe8fe6a47b2a8eac178cf2ad6e9,
title = "Phase I study of paclitaxel given by seven-week continuous infusion concurrent with radiation therapy for locally advanced squamous cell carcinoma of the head and neck",
abstract = "Purpose: Paclitaxel is one of the most active agents for squamous cell carcinoma of the head and neck (SCCHN) and an in vitro radiosensitizer. The dose-response relationship for paclitaxel may depend more on exposure duration than on peak concentration. This National Cancer Institute-sponsored phase I trial was designed to determine the feasibility of combining continuous-infusion (CI) paclitaxel with concurrent radiation therapy (RT). Patients and Methods: Patients with previously untreated stage IVA/B SCCHN were eligible. Primary end points were determination of the maximum-tolerated dose, dose-limiting toxicity, and pharmacokinetics for paclitaxel given by CI (24 hours a day, 7 days a week for 7 weeks) during RT (70 Gy/7 weeks). Results: Twenty-seven patients were enrolled and assessable for toxicity. Nineteen of the patients who completed ≥ 70 Gy were assessable for response. Grade 3 skin and mucosal acute reactions occurred at 10.5 mg/m2/d, but uninterrupted treatment was possible in five of six patients. At 17 mg/m2/d, skin toxicity required a 2-week treatment break for all three patients. The mean paclitaxel serum concentration at dose levels ≥ 6.5 mg/m2/d exceeded that reported to achieve in vitro radiosensitization. Initial locoregional control was achieved in 14 (58{\%}) of 24 of patients treated to 70 Gy, and control persisted in nine (38{\%}). Conclusion: CI paclitaxel with concurrent RT is a feasible and tolerable regimen for patients with advanced SCCHN and good performance status. Preliminary response and survival data are encouraging and suggest that further study is indicated. The recommended phase II dose of paclitaxel by CI is 10.5 mg/m2/d with RT for SCCHN.",
author = "Rosenthal, {D. I.} and Lee, {J. H.} and R. Sinard and Yardley, {D. A.} and M. Machtay and Rosen, {D. M.} and Egorin, {M. J.} and Weber, {R. S.} and Weinstein, {G. S.} and Chalian, {A. A.} and Miller, {L. K.} and Frenkel, {E. P.} and Carbone, {D. P.}",
year = "2001",
month = "3",
day = "1",
language = "English (US)",
volume = "19",
pages = "1363--1373",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "5",

}

TY - JOUR

T1 - Phase I study of paclitaxel given by seven-week continuous infusion concurrent with radiation therapy for locally advanced squamous cell carcinoma of the head and neck

AU - Rosenthal, D. I.

AU - Lee, J. H.

AU - Sinard, R.

AU - Yardley, D. A.

AU - Machtay, M.

AU - Rosen, D. M.

AU - Egorin, M. J.

AU - Weber, R. S.

AU - Weinstein, G. S.

AU - Chalian, A. A.

AU - Miller, L. K.

AU - Frenkel, E. P.

AU - Carbone, D. P.

PY - 2001/3/1

Y1 - 2001/3/1

N2 - Purpose: Paclitaxel is one of the most active agents for squamous cell carcinoma of the head and neck (SCCHN) and an in vitro radiosensitizer. The dose-response relationship for paclitaxel may depend more on exposure duration than on peak concentration. This National Cancer Institute-sponsored phase I trial was designed to determine the feasibility of combining continuous-infusion (CI) paclitaxel with concurrent radiation therapy (RT). Patients and Methods: Patients with previously untreated stage IVA/B SCCHN were eligible. Primary end points were determination of the maximum-tolerated dose, dose-limiting toxicity, and pharmacokinetics for paclitaxel given by CI (24 hours a day, 7 days a week for 7 weeks) during RT (70 Gy/7 weeks). Results: Twenty-seven patients were enrolled and assessable for toxicity. Nineteen of the patients who completed ≥ 70 Gy were assessable for response. Grade 3 skin and mucosal acute reactions occurred at 10.5 mg/m2/d, but uninterrupted treatment was possible in five of six patients. At 17 mg/m2/d, skin toxicity required a 2-week treatment break for all three patients. The mean paclitaxel serum concentration at dose levels ≥ 6.5 mg/m2/d exceeded that reported to achieve in vitro radiosensitization. Initial locoregional control was achieved in 14 (58%) of 24 of patients treated to 70 Gy, and control persisted in nine (38%). Conclusion: CI paclitaxel with concurrent RT is a feasible and tolerable regimen for patients with advanced SCCHN and good performance status. Preliminary response and survival data are encouraging and suggest that further study is indicated. The recommended phase II dose of paclitaxel by CI is 10.5 mg/m2/d with RT for SCCHN.

AB - Purpose: Paclitaxel is one of the most active agents for squamous cell carcinoma of the head and neck (SCCHN) and an in vitro radiosensitizer. The dose-response relationship for paclitaxel may depend more on exposure duration than on peak concentration. This National Cancer Institute-sponsored phase I trial was designed to determine the feasibility of combining continuous-infusion (CI) paclitaxel with concurrent radiation therapy (RT). Patients and Methods: Patients with previously untreated stage IVA/B SCCHN were eligible. Primary end points were determination of the maximum-tolerated dose, dose-limiting toxicity, and pharmacokinetics for paclitaxel given by CI (24 hours a day, 7 days a week for 7 weeks) during RT (70 Gy/7 weeks). Results: Twenty-seven patients were enrolled and assessable for toxicity. Nineteen of the patients who completed ≥ 70 Gy were assessable for response. Grade 3 skin and mucosal acute reactions occurred at 10.5 mg/m2/d, but uninterrupted treatment was possible in five of six patients. At 17 mg/m2/d, skin toxicity required a 2-week treatment break for all three patients. The mean paclitaxel serum concentration at dose levels ≥ 6.5 mg/m2/d exceeded that reported to achieve in vitro radiosensitization. Initial locoregional control was achieved in 14 (58%) of 24 of patients treated to 70 Gy, and control persisted in nine (38%). Conclusion: CI paclitaxel with concurrent RT is a feasible and tolerable regimen for patients with advanced SCCHN and good performance status. Preliminary response and survival data are encouraging and suggest that further study is indicated. The recommended phase II dose of paclitaxel by CI is 10.5 mg/m2/d with RT for SCCHN.

UR - http://www.scopus.com/inward/record.url?scp=0035281499&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035281499&partnerID=8YFLogxK

M3 - Article

VL - 19

SP - 1363

EP - 1373

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 5

ER -