Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma.
OBJECTIVE
To define favorable pretreatment characteristics for overall survival (OS), progression-free survival (PFS), locoregional control, and freedom from distant metastasis for patients with recurrent and second primary head-and-neck cancer treated with concomitant chemotherapy and reirradiation.


METHODS
Our study population comprised a subset of 115 previously irradiated patients without overt metastases from 304 poor-prognosis head-and-neck cancer patients treated in seven consecutive phase I-II protocols. Of the 115 patients, 49, who had undergone surgical resection, were treated with a median of four cycles of concurrent chemotherapy and reirradiation and 66, who had not undergone surgical resection, were treated with a median of five cycles. The following regimens were used: 5-fluorouracil and hydroxyurea concurrent with reirradiation (FHX) (n=14), cisplatin plus FHX (n=23), paclitaxel plus FHX (n=42), gemcitabine plus paclitaxel and 5-fluorouracil concurrent with reirradiation (n=26), and irinotecan plus FHX (n=10).


RESULTS
The median lifetime radiation dose was 131 Gy. The median follow-up for surviving patients was 67.4 months (range, 18.5-158.7). The median OS and PFS was 11 and 7 months (range, 0.2-158.7), respectively. The 3-year OS, PFS, locoregional control, and freedom from distant metastasis rate was 22%, 33%, 51%, and 61%, respectively. Multivariate analysis identified reirradiation dose, triple agent (cisplatin-, paclitaxel-, or gemcitabine-containing chemotherapy), and surgery before protocol treatment as independently prognostic for OS, PFS, and locoregional control. Triple-agent chemotherapy was prognostic for freedom from distant metastasis. Nineteen patients died of treatment-related toxicity, five of these of carotid hemorrhage.


CONCLUSIONS
For recurrent and second primary head-and-neck cancer, trimodality therapy with surgery, concurrent chemotherapy, and reirradiation for a full second dose offers potential for long-term survival. Owing to the substantial toxicity and lack of an optimal regimen, reirradiation of recurrent head-and-neck cancer should be limited to clinical trials.
Salama
Joseph K
JK
Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, IL 60637-1470, USA.
Vokes
Everett E
EE
Chmura
Steven J
SJ
Milano
Michael T
MT
Kao
Johnny
J
Stenson
Kirsten M
KM
Witt
Mary Ellyn
ME
Haraf
Daniel J
DJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D000077146:Irinotecan; D008297:Male; D008336:Mandibular Diseases / Q000601:surgery; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D016609:Neoplasms, Second Primary / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D010025:Osteoradionecrosis / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D011879:Radiotherapy Dosage; D017211:Treatment Failure; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D000077146:Irinotecan; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; D006918:Hydroxyurea; D002166:Camptothecin; D000093542:Gemcitabine