Induction paclitaxel, carboplatin, and infusional 5-FU followed by concurrent radiation therapy and weekly paclitaxel/carboplatin in the treatment of locally advanced head and neck cancer: a phase II trial of the Minnie Pearl Cancer Research Network.
OBJECTIVE
The purpose of this study was to evaluate the feasibility, toxicity, and efficacy of a novel combined-modality treatment for patients with locally advanced squamous carcinoma of the head and neck.


METHODS
In this multicenter, community-based phase 11 study, 123 previously untreated patients with locally advanced squamous carcinoma of the head and neck received 6 weeks of induction chemotherapy followed by concurrent high-dose radiation therapy and weekly chemotherapy. Induction chemotherapy included paclitaxel (200 mg/m2, 1-hour i.v. infusion) on days 1 and 22, carboplatin (AUC 6.0 i.v.) on days 1 and 22, and 5-fluorouracil (225 mg/m2 per day, 24-hour continuous i.v. infusion) on days 1-43. After 1 week without therapy, radiation therapy, 1.8 Gy/day, 5 days weekly, to a total dose of 68.4 Gy, was administered to the primary site and the bilateral cervical lymph nodes. During radiation therapy, patients also received six weekly doses of paclitaxel (50 mg/m2, 1-hour i.v. infusion) and carboplatin (AUC 1.0 i.v). After completion of therapy, patients were restaged with computed tomographic and endoscopic examination; patients in complete remission were followed up without further treatment.


RESULTS
One hundred twenty-three patients (74% with stage IV disease) entered this trial, and 111 patients (90%) completed the entire treatment course. Seventy of 116 evaluable patients (60%; 95% Cl, 51%-69%)had a clinical complete response to treatment. After a median follow-up of 24 months, the 2-and 3-year actuarial survivals were 66% and 51%, respectively. Local toxicity was moderately severe during combined-modality therapy; however, xerostomia has been the only frequent chronic toxicity of this program.


CONCLUSIONS
This novel combined-modality treatment program, containing paclitaxel and avoiding the use of cisplatin, is feasible, is highly active, and can be administered with acceptable toxicity in a community-based setting. Aggressive nutritional support should be considered in patients receiving this regimen, to improve acute palliation and to maximize the delivery of combined-modality therapy. Further evaluation of this treatment program is warranted. Incorporation of various novel biologic agents, particularly the epidermal growth factor receptor antagonists, may further improve efficacy.
Sarah Cannon Cancer Center, Nashville, TN 37203, USA.
John D
JD
Hainsworth
Anthony A
AA
Meluch
Suzanne
S
McClurkan
James R
JR
Gray
Steven L
SL
Stroup
Howard A
HA
Burris
Denise A
DA
Yardley
James E
JE
Bradof
Kathleen
K
Yost
James K
JK
Ellis
F Anthony
FA
Greco
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002173:Cancer Care Facilities; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D019058:Community Networks; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011832:Radiation Injuries; D011879:Radiotherapy Dosage; D011882:Radiotherapy, High-Energy; D015996:Survival Rate
D016190:Carboplatin; D017239:Paclitaxel; D005472:Fluorouracil