Induction chemotherapy with cisplatin, fluorouracil, and high-dose leucovorin for squamous cell carcinoma of the head and neck: long-term results.

PURPOSE: A phase II trial of cisplatin, fluorouracil, and leucovorin (PFL) induction chemotherapy in patients with locally advanced squamous cell carcinomas of the head and neck region (HNCA). PATIENTS AND METHODS: One hundred two patients (stage III/IV, previously untreated) were treated with induction PFL. Patients with resectable primary tumor site lesions and clinical complete response (CR) were offered radiotherapy (RT) without surgery to the primary tumor site. Response, toxicity, local-regional therapy, survival, and preservation of the primary tumor site were assessed. RESULTS: Among 279 courses, the overall response rate was 81%. Nineteen (19%) failed to respond, including three who died during therapy. Sixty-seven (69%) of 97 with assessable primary lesions had a clinical CR at the primary tumor site. Pathologic CR was recorded in 46 of 55 (84%) clinical CR patients who had biopsies performed on the primary tumor site. Toxicities resulted in unexpected hospitalizations in 19% of cases. After definitive local-regional therapy, 84 (82%) were disease-free including 71 (69%) with preserved primary tumor site anatomy. With a median follow-up time of 63 months, the cause-specific, overall (OS), and failure-free survival (FFS) rates at 5 years are 58%, 52%, and 51%. Local failure occurred in 29 of 102 (29%) and the local control rate at 5 years was 68%. CONCLUSION: PFL has significant activity with acceptable toxicity in patients with advanced disease who have a good performance status. Preservation of the primary tumor site could be achieved without apparent loss of local control or survival. Management of neck disease by surgery or RT must be individualized and separate from management of primary tumor. Survival compares favorably with similar trials of induction chemotherapy or chemoradiotherapy.

Docetaxel: an active drug for squamous cell carcinoma of the head and neck.

PURPOSE: We conducted a phase II study designed to evaluate the activity, safety, and tolerability of docetaxel (Taxotere: Rhône-Poulenc Rorer Pharmaceuticals Inc, Collegeville, PA) in patients with advanced, incurable, or recurrent squamous cell carcinoma of the head and neck (SCCHN) who had not received prior palliative chemotherapy. PATIENTS AND METHODS: Thirty-one patients with measurable, locoregional, or metastatic SCCHN were treated with docetaxel, administered at a dose of 100 mg/m2 as a 1-hour intravenous (i.v.) infusion once every 21 days on an outpatient basis. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Prophylactic administration of growth factors or antiemetics was not permitted. RESULTS: Thirty-one patients were treated. Twenty-nine patients were assessable for response and 30 for toxicity. Four of 31 patients (13%) achieved complete response (CR), nine (29%) achieved partial response had stable disease (SD) and seven (23%) experienced progression of disease (PD). The major response rate was 42% (95% confidence interval [CI], 24% to 60%). The median duration of responses was 5 months (range, 2 to 14). The principal toxicity was leukopenia, which occurred with rapid onset and brief duration. Sixteen patients (53%) experienced nadir fever, and 13 required dose reduction. Hypersensitivity reactions occurred in four patients. Grade 3 peripheral neuropathy occurred in two patients; grade 2 or 3 fatigue occurred in six (20%) and 10 (33%), respectively. Minimal edema (grade 1) occurred in five patients (17%). Clinically significant mucositis, diarrhea, or dermatitis were not observed. CONCLUSION: Docetaxel has major activity against SCCHN. It appears to be well tolerated in this group of patients and can be safely administered on an outpatient basis. Premedication with dexamethasone, cimetidine, and diphenhydramine is associated with a reduced incidence of significant edema, hypersensitivity reactions, and dermatologic toxicities.

Terminal duct carcinoma. Recognition of a low-grade salivary adenocarcinoma.

We describe six cases of terminal duct carcinoma of the minor salivary glands. All were localized to the oral cavity, without regional nodal or distant metastases. Histologically, five were originally mistaken for adenoid cystic carcinoma; one was interpreted as monomorphic adenoma with areas of adenoid cystic carcinoma. Treatment consisted of wide resection with or without radiation therapy, with no incidence of recurrence or metastasis. The characteristics of this recently described pathologic entity are reviewed. The less aggressive behavior of this tumor compared with adenoid cystic carcinoma should call for less radical therapy, with a favorable prognosis in most cases. Recognition of this tumor as a distinct clinical and pathologic entity is therefore important.

Primary site management following induction chemotherapy with cis-platinum, 5-fluorouracil, and leucovorin.

A phase II clinical trial was initiated in 1987 to evaluate a new induction regimen of cis-platinum, 5-fluorouracil, and leucovorin (PFL) for patients with stages III-IV squamous cell carcinoma of the head and neck. Ninety patients were treated and followed for a median duration of 18 months. The median age was 55 and 87% of the patients had stage IV disease. The rates of complete and overall clinical response following three cycles of PFL were 57% and 80%, respectively; the rate of complete response at the primary site was 72%. Eighty-four percent of patients were treated to the primary site with radiation alone (median dose 68 Gy in daily 1.8-Gy fractions) irrespective of the location of the primary site or initial T-stage. The acute tolerance to full-course radiation following PFL was acceptable. The actuarial rate of primary site control for patients treated with radiation was 67% at 36 months. An important prognostic indicator for primary site control was a complete clinical response to induction PFL. For patients who achieved a complete response, radiation or surgery followed by radiation controlled primary site disease equally well at 70%. Patients with a partial response did less well. For these patients, surgery and radiation appeared slightly better than radiation alone.

Continuous infusion high-dose leucovorin with 5-fluorouracil and cisplatin for untreated stage IV carcinoma of the head and neck.

STUDY OBJECTIVE: To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck. DESIGN: Nonrandomized, prospective trial. SETTING: A comprehensive cancer center. PATIENTS: Thirty-five patients (4 patients [11%], stage III; 31 patients [89%], stage IV [MO]), all evaluable for response and toxicity. INTERVENTIONS: Two to three cycles of PFL before definitive, local-regional therapy (surgery and radiation therapy or radiation therapy alone). Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2 body surface area daily, days 1 through 5); 5-fluorouracil (800 mg/m2 body surface area daily, days 2 through 6); and leucovorin (500 mg/m2 body surface area daily, days 1 through 6) administered once every 28 days. Pathologic response was evaluated by surgical resection or biopsy. Serum-reduced folates were measured before and 18 hours after the initiation of chemotherapy. RESULTS: A clinical response to PFL was achieved in 28 of 35 (80%) patients: 23 (66%) patients had a complete response (90% CI, 50% to 79%) and 5 (14%) patients, a partial response. A complete response was confirmed pathologically in 14 of 19 (74%) patients. The most common toxicity was mucositis (grade 2 to 3; 94% of patients). Dose reduction for toxicity was necessary in 11 (31%) patients. There were no treatment-related deaths. Serum levels of leucovorin and (6S)5-methyltetrahydrofolate were measured in 7 patients. After 18 hours, the mean leucovorin level (+/- SD) was 34.3 +/- 1.5 mumol/L, of which only 8.0 +/- 0.5% was the active 6S isomer. The mean serum (6S)5-methyltetrahydrofolate was 9.2 +/- 0.6 mumol/L. CONCLUSIONS: Continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin is a new and highly active chemotherapy regimen that can achieve clinical and pathologically confirmed complete responses in a substantial proportion of patients with advanced, local-regional squamous cell carcinoma of the head and neck. Further studies are needed to confirm the activity of PFL and to determine its potential impact on local tumor control and disease-free and overall survival.

Otolaryngological manifestations of the Stickler syndrome.

The Stickler syndrome is a dominantly inherited, connective tissue disorder associated with retinal detachments, joint and skeletal abnormalities, and characteristic facies. We wished to evaluate patients with this disorder to ascertain the frequency of otolaryngological manifestations. Fourteen patients, 4-17 years of age, were evaluated when admitted for retinal detachment. Findings included: midface hypoplasia in all patients; mandibular hypoplasia in 11 patients; palatal anomalies in 10 patients (frank cleft in 6, submucous cleft in two, highly arched palate in two); and hearing loss in 6 patients (mixed loss in 3, sensorineural loss in 3). Hearing loss appeared more commonly in the higher frequencies; no apparent correlation was found between the presence of hearing loss and orofacial anomalies. Our experience suggests that the Stickler syndrome is not rare. Craniofacial dysmorphic features and otologic findings are sufficiently frequent to warrant otolaryngological evaluation.