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.
Hainsworth
John D
JD
Sarah Cannon Cancer Center, Nashville, TN 37203, USA.
Meluch
Anthony A
AA
McClurkan
Suzanne
S
Gray
James R
JR
Stroup
Steven L
SL
Burris
Howard A
HA
Yardley
Denise A
DA
Bradof
James E
JE
Yost
Kathleen
K
Ellis
James K
JK
Greco
F Anthony
FA
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