Phase II evaluation of 96-hour paclitaxel infusion in advanced (recurrent or metastatic) squamous cell carcinoma of the head and neck (E3395): a trial of the Eastern Cooperative Oncology Group.
BACKGROUND
Paclitaxel (24-hour infusion) has yielded activity in advanced squamous cell carcinoma of the head and neck (SCCHN). Protracted exposure to paclitaxel may overcome resistance observed by using shorter infusions. Therefore we sought to evaluate paclitaxel by 96-hour infusion in both treatment-naïve and previously treated patients with SCCHN.


METHODS
Eligibility stipulated bi-dimensionally measurable, biopsy-documented, incurable SCCHN, Eastern Cooperative Oncology Group performance status (PS) 0-1, and adequate physiological indices. Patients were divided into three cohorts: 1) chemotherapy-naïve; 2) chemotherapy-exposed, paclitaxel-naïve; and 3) chemotherapy and paclitaxel exposed. Paclitaxel was dosed at 140 mg/m2 (96-hour infusion) every 3 weeks in treatment-naïve patients and at 120 mg/m2 (96 hours) every 3 weeks in previously treated patients.


RESULTS
Fifty patients were accrued between February 1997 and July 2000. The study was terminated because of low response rate. Eighty percent of patients were male, 75% PS 1. Nearly half the patients had oropharyngeal or hypopharyngeal primary sites. There was one treatment-related death due to neutropenic fever/pneumonia. Grade 4 toxicities included granulocytopenia in eight patients (20%), thrombocytopenia, and stomatitis in one patient each. Grade 3 or greater anemia occurred in 10 patients. There was no grade 2 or 3 peripheral sensory neuropathy. In 15 chemotherapy-naïve patients, two responses (13%) were observed. There were no responses in treatment-exposed patients. The overall median survival was 5.5 months, and 1-year survival rate 10%. Treatment-naïve patients had a median survival of 8.2 months and 1-year survival rate of 20%.


CONCLUSIONS
Paclitaxel by 96-hour infusion at a dose of 120-140 mg/m2/96 hours is only marginally active in the treatment of SCCHN. This dose and schedule cannot be recommended for further evaluation.
Langer
Corey J
CJ
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. cj_langer@fccc.edu
Li
Yi
Y
Jennings
Timothy
T
DeConti
Ronald C
RC
Nair
Suresh
S
Cohen
Roger B
RB
Forastiere
Arlene A
AA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D015331:Cohort Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D017239:Paclitaxel / Q000008:administration & dosage*; D015996:Survival Rate
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel