title: A phase I/II study of paclitaxel plus cisplatin as first-line therapy for head and neck cancers: preliminary results.
abstract: Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.
authors.affiliation: Division of Medical Oncology, Hospital Universitario Doce de Octubre, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Hitt
authors.forename: J
authors.initials: J
authors.lastname: Hornedo
authors.forename: R
authors.initials: R
authors.lastname: Colomer
authors.forename: C
authors.initials: C
authors.lastname: Mendiola
authors.forename: A
authors.initials: A
authors.lastname: Brandariz
authors.forename: E
authors.initials: E
authors.lastname: Sevilla
authors.forename: J
authors.initials: J
authors.lastname: Alvarez-Vicent
authors.forename: H
authors.initials: H
authors.lastname: Cortés-Funes
mesh_terms: D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018771:Arthralgia / Q000139:chemically induced; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D010292:Paresthesia / Q000139:chemically induced; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel; D002945:Cisplatin