title: Concurrent paclitaxel, carboplatin, and radiotherapy in advanced head and neck cancers: a phase II study--preliminary results.
abstract: Radiotherapy or surgery alone for advanced head and neck cancer generally yields poor results. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin have both shown excellent radiosensitization through two discrete mechanisms, namely, blocking the cell cycle in the G2/M phase and inhibiting DNA repair. In an effort to improve locoregional control and survival, a prospective phase II study was initiated using paclitaxel 60 mg/ml and carboplatin (area under the concentration-time curve of 1), each given as a single dose weekly with concurrent conventional fractionated external beam radiotherapy. Patients were stratified into two groups: operable and inoperable/unresectable. The operable and inoperable groups received 5 weeks (45 Gy) and 8 weeks (72 Gy) of chemoradiotherapy, respectively. Patients in the operable group were evaluated with repeat biopsies from the primary site after 5 weeks. Those with a positive biopsy underwent surgery; those with a negative biopsy received 3 additional weeks of chemoradiotherapy. Thirty-four patients were entered in the operable group (28 men and six women; 40 to 71 years of age; 12 stage III and 22 stage IV). Of 26 evaluable patients, 19 (73%) had a complete clinical response (95% confidence interval [CI], 52% to 88%) and six (23%) had a partial response (95% CI, 9% to 44%), for a total clinical response rate of 96% (95% CI, 80% to 100%). A pathologic complete response at the primary site (two had an unknown primary site) occurred in 17 of 24 (71%) patients (95% CI, 49% to 87%). Of 20 patients with N1-3 nodes who underwent neck dissection, 17 (85%) had pathologically negative lymph nodes. Seven patients with residual tumor at the primary site were resected (oral cavity, three; maxilla, one; base of tongue, one; and larynx, two). Grades 3 and 4 mucositis were seen in 19 (73%) patients; mucositis was the most common and significant morbidity. Accrual for the inoperable group continues. Concomitant paclitaxel, carboplatin, and external beam radiotherapy yielded excellent clinical responses, but produced significant grade 3/4 toxicity. In the operable group, the majority of responders had a complete pathologic response. These preliminary findings will be assessed in terms of response duration, organ preservation, and long-term survival.
authors.affiliation: Department of Radiation Oncology, Brown University School of Medicine, Rhode Island Hospital, Providence 02903, USA.
authors.forename: P
authors.initials: P
authors.lastname: Chougule
authors.forename: H
authors.initials: H
authors.lastname: Wanebo
authors.forename: W
authors.initials: W
authors.lastname: Akerley
authors.forename: R
authors.initials: R
authors.lastname: McRae
authors.forename: P
authors.initials: P
authors.lastname: Nigri
authors.forename: L
authors.initials: L
authors.lastname: Leone
authors.forename: H
authors.initials: H
authors.lastname: Safran
authors.forename: N
authors.initials: N
authors.lastname: Ready
authors.forename: R J
authors.initials: RJ
authors.lastname: Koness
authors.forename: K
authors.initials: K
authors.lastname: Radie-Keane
authors.forename: B
authors.initials: B
authors.lastname: Cole
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D016190:Carboplatin / Q000008:administration & dosage* / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000633:toxicity; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D016190:Carboplatin; D017239:Paclitaxel