Computed tomographic density of metastatic lymph nodes as a treatment-related prognostic factor in advanced head and neck cancer.

Pretherapeutic identification of patients likely to benefit from neoadjuvant chemotherapy for head and neck epidermoid cancer is of interest. We retrospectively analyzed the pretherapeutic computed tomographic (CT) scans of lymph nodes of 70 patients with head and neck cancer. All 70 patients were clinically classified as having stage IV disease. The purpose of our analysis was to compare the prognostic value of CT node density with that of the following factors: age, T and N categories, Eastern Cooperative Oncology Group performance status, tumor site, histopathologic type of disease [squamous cell carcinoma (SCC) or undifferentiated carcinoma of nasopharyngeal type (UNCT)], and type of local-regional treatment. A simple two-grade nodal density grading system was devised. The density of normal adjacent muscle was chosen as the density standard. A node was classified grade 1 if less than 33% of the node consisted of hypodense zones. A node was classified grade 2 if more than 33% of the node consisted of hypodense zones. Patients with grade 1 nodes had a complete response rate of 68% (21/31) compared with 8% (3/39) for those with grade 2 nodes (P less than .0001). The only other factor associated with complete node response was UCNT (P less than .03). However, node density remained the significant prognostic factor after adjustment for histopathologic type. Follow-up ranged from 16 to 44 months, with a median of 29 months. Patients with grade 1 nodes had a median survival time of 32 months versus 13 months for those with grade 2 nodes (P less than .01). A prospective study should validate the prognostic value of CT node density and its possible use in determining optimal multimodal therapy for advanced head and neck cancers.

Intensive concomitant chemoradiotherapy in locally advanced unresectable squamous cell carcinoma of the head and neck: a phase II study of radiotherapy with cisplatin and 7-week continuous infusional fluorouracil.

PURPOSE: To evaluate an intensive concomitant chemoradiotherapy protocol of conventional radiotherapy with intermittent cisplatin (CDDP) and continuous-infusion fluorouracil (5-FU) in unresectable, locally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Fifty-seven patients with unresectable stage IV MO disease (International Union Against Cancer [UICC]/American Joint Committee on Cancer [AJCC], 1987) received radiotherapy 70 Gy followed by CDDP 80 mg/m2 and 5-FU 300 mg/m2/d. Response was assessed 2 months after treatment completion. RESULTS: Thirty patients (52%) received the full treatment schedule; 53 (93%) received full-dose radiotherapy, while 48 (84%) were given at least 75% of the planned chemotherapy doses. Severe mucositis (World Health Organization [WHO]) grade 3 to 4 was the limiting toxicity and was seen in 79% of patients. The median time for mucositis resolution was 8 weeks. Other toxicities were generally manageable, but there were four treatment related deaths (7%). Fifty patients were assessable for activity, with an overall response rate of 70% (95% confidence interval [CI], 58% to 82%). Complete response (CR) and partial response (PR) rates were 42% and 28%, respectively. CONCLUSION: This simultaneous combined-modality regimen was feasible at the cost of severe mucosal toxicity, which required hospitalization with nutritional, parenteral, and hydroelectrolytic support. The high response rate achieved (70%) did not translate into improved survival, probably due to patient eligibility. The likelihood of cure of this high-tumoral-volume patient population remains low (approximately 10%), despite the association of two therapeutic modalities at full standard therapeutic intensity.

Recurrent and/or metastatic head and neck squamous cell carcinoma: a clinical, univariate and multivariate analysis of response and survival with cisplatin-based chemotherapy.

One hundred two patients with recurrent and/or metastatic head and neck squamous cell cancer were entered into four consecutive phase II trials, all cisplatinum (C-DDP, 100 mg/m2/cycle)-based. The two combinations tried were C-DDP, bleomycin, and fluorouracil (CFB) on 54 patients, and cisplatinum and vindesin in 36 patients (CV). The CFB combination was given with C-DDP by continuous infusion over 96 hours (23 patients) or on day 1 (31 patients). The CV regimen was also given in two different schedules, with VDS at 3 mg/m2/g weekly (12 patients) or by a 96-hour continuous infusion (0.6 to 1.0 mg/m2/d) in 24 patients. The following variables: sex, age, performance status, previous therapy, local recurrence, length of disease-free interval (DFI), distant metastases, weight loss, primary site, histological differentiation, type of chemotherapy, previous chemotherapy, evaluable/measurable disease, erythrosedimentation rate, and their relation with response to chemotherapy (WHO) and survival were submitted to both univariate and multivariate analysis (Cox). Overall response rate (RR:CR + PR) was 25 (28%) of 90. In the CFB protocols, RR was 12 (22%) of 54 vs. 13 (38%) of 36 (P = 0.15, NS) in the CV combination group. For the four different combinations the RR was CFB C-DDPci 7 (30%) of 23, CFB C-DDP 1 hour 5 (16%) of 31, CV VDS weekly 2 (17%) of 12, CV VDSci 11 (45%) of 24. The patient populations were very different, with the latest combination consisting of metastatic patients exclusively. Univariate analysis of multiple variables showed age less than 60 years, PS:0 or 1, no previous therapy, absence of local relapse, metastatic disease, long DFI, and that measurable disease was significant for the probability of response. Median survival was 7 months for the 90 evaluated patients, 5 months for nonresponders, and 9 months for responders (P = 0.01). In the univariate analysis, significant factors for survival were PS:0 or 1, a weight loss below 10%, long DFI, response to chemotherapy, erythrosedimentation rate (ESR) of less than 30 mm/1st hr, presence of bone metastasis, and the number of metastases. Multivariate analysis shows PS, the absence of local relapse, and disease-free interval as significant prognostic factors for response. Multivariate analysis factors of significance for survival were PS, weight loss, and response to chemotherapy. The analysis of the clinical pattern showed an evolution in RR from 3 (8%) of 36 on previously irradiated local recurrent disease to 8 (73%) of 11 in previously untreated patients with metastatic disease at presentation.(ABSTRACT TRUNCATED AT 400 WORDS)

Neoadjuvant chemotherapy in multiple synchronous head and neck and esophagus squamous cell carcinomas.

A consecutive series of 22 patients with multiple synchronous squamous cell carcinomas of the upper aerodigestive tract was retrospectively reviewed. These patients were treated initially with cis-platinum combination chemotherapy before definitive locoregional therapy (surgery and/or radiation therapy). Sixteen of 21 patients had simultaneous head and neck and esophageal primaries, 3 patients had multiple synchronous head and neck primaries, 2 patients had head and neck (HN) and a bronchial epidermoid cancer, and 1 patient had simultaneous esophageal and bronchial carcinomas of epidermoid lineage. Sixteen (77%) of the 21 patients responded to chemotherapy in all the tumor sites evaluated, and a clinically complete response was obtained in 6 (29%). After definitive locoregional treatment, the complete local control rate was 68%, with 34 complete responses for 50 primary tumor sites in 21 patients. Twelve patients were free of disease after locoregional treatment. Six patients are still alive 27 to 57 months after complementary definitive locoregional treatment and a minimum follow-up of 27 months. Median survival for the overall group is 17 months. The response to chemotherapy is remarkable, which may be due to the small tumoral volume present in many of the cases (T1 to T2). Nevertheless, the present report stresses the importance of an aggressive combined therapeutic approach in this difficult clinical situation.

Low toxicity with continuous infusion of high-dose bleomycin in poor prognostic testicular cancer.

Bleomycin is a powerful antitumoral antibiotic whose utilization has been limited by pulmonary toxicity. At the Medical Oncology Department of the Hospital General de Mexico, SS, 17 patients with high-risk testicular cancer were treated with therapeutic regimens based on cisplatin and bleomycin in continuous infusion. The mean bleomycin dose was 813 mg. Adequate renal function was observed in all patients during and after chemotherapy. During a minimum 4-year follow-up period, no patient experienced pulmonary toxicity; 3 patients died due to tumoral progression. The remaining 14 patients are alive and none of them had shown x-ray abnormalities nor a significant reduction in pulmonary vital capacity (PVC) or carbon monoxide diffusion capacity (DLCO). Bleomycin in continuous infusion can be an appropriate alternative for reducing pulmonary toxic effects. Therefore, randomized controlled studies should be conducted in order to determine if this treatment regime could enhance the therapeutic index.

Phase II study of cisplatin and continuous-infusion 5-fluorouracil and bleomycin for recurrent and metastatic head and neck squamous-cell carcinoma.

5-Fluorouracil (5-FU) and bleomycin (BLM) are active agents in head and neck squamous-cell cancer (H-N-scc). Less toxicity and an enhanced activity have been reported when these agents are administered by continuous infusion (CI), with or without a bolus of cisplatin (CDDP), another active agent. Thirty-three patients with recurrent and/or metastatic head and neck squamous cell carcinoma were treated with a combination regimen including CDDP (100 mg/m2) on day 1 plus BLM (15-mg bolus followed by 16 mg/m2/day by CI) and 5-FU (650 mg/m2/day by CI) on days 1-5 every 3 weeks. Thirty-one patients were evaluable for toxicity and response. The response rate (RR) was 15% (5 of 31), with one complete response (CR) and four partial responses (PRs), at a confidence interval of 95% (0-34%). Four of the five responders had not received previous radiotherapeutic treatment. Toxicity was deemed acceptable; nausea and vomiting and stomatitis were moderate. Only one patient had irreversible renal toxicity, after two cycles of chemotherapy. No symptomatic lung toxicity was observed. Good antitumour activity was noted for previously untreated disease (3 of 4; 75% RR). This combination of drugs proved to be inactive, however, in previously irradiated recurrent and/or metastatic H-N-scc (1 of 25; 4% RR). These results underscore the need to be extremely attentive to different patient populations when selecting therapeutic schedules and when analyzing reported results.

A phase II study of cisplatin and continuous infusion of vindesine in metastatic head and neck squamous cell cancer.

The chemotherapeutic treatment of recurrent and/or metastatic squamous cell carcinoma (SCC) of the head and neck (H & N) has a very dismal prognosis, with survival usually not exceeding 1 year. Reported objective response rates vary between 3% and 70%. This difference appears largely attributable to the heterogeneity of the patient populations included in most published Phase II studies in H & N cancer. They usually include together initially metastatic, recurrent, and post primary treatment metastatic disease patients. These patients respond differently to chemotherapy. Because of this situation, we decided to study a more homogeneous patient population consisting of metastatic patients only. Cisplatin (CDDP) and vindesine (VDS) are active agents in H & N SCC. As VDS has a cycle-specific activity, the therapeutic index may be increased if it is administered in a continuous infusion (CI) schedule. Thirty-three patients with metastatic H & N (69% biopsy proven) were treated with a combination regimen including CDDP (100 mg/m2) day 1 and VDS 0.6 to 1 mg/m2 for 96 hours of CI. Thirty-one patients were evaluable for response: five had a complete response (CR; 16%) and 11 had a partial response (PR; 36%) with an overall rate response of 52% (95% confidence limit: 33% to 70%). Median duration of CR was 6.4 months (3 to 19 months) and 4.4 months for PR (3 to 6 months). A decrease in the leukocytes was the main toxicity encountered with this regimen. This combination regimen containing CDDP and CI VDS was well tolerated and active in H & N SCC. The incorporation of an active vinca-alkaloid in neoadjuvant regimens should be considered.

Neoadjuvant chemotherapy consisting of cisplatin and continuous infusions of bleomycin and 5-fluorouracil for advanced head and neck cancer. The need for a new stratification for stage IV (M0) disease.

A Phase II study of cisplatin (100 mg/m2 on day 1) and bleomycin (15 mg intravenous push day 1) followed by 5 days of continuous intravenous infusions of 5-fluorouracil (5-FU) (650 mg/m2/d) and bleomycin (16 mg/m2/d) repeated at 21-day intervals was performed in 54 previously untreated patients with nonmetastatic (M0), locoregionally advanced head and neck squamous cell carcinoma (SCC). The aim of this study was to increase the complete response rate to chemotherapy and to identify prognostic factors that may influence local control and disease-free survival. From April 1986 until August 1988, 5 patients with Stage III and 49 with Stage IV (International Union Against Cancer-American Joint Committee on Cancer 1986 [UICC-AJCC]) disease received this regimen. Thirty (61%) patients with Stage IV disease had bulky nodal disease (9 N2c and 21 N3) and 29 (53%) had T4 primary lesions. The response rate was 59% (95% confidence interval, 47% to 71%) and the complete response rate to chemotherapy was 13% (95% confidence interval, 0% to 26%). The response rate was greatly influenced by tumoral volume and performance status (PS). The complete response rate to chemotherapy was 40% for patients with Stage III disease (2 of 5 patients) versus 10% for patients with Stage IV disease (5 of 49 patients; P = 0.02). The response rate for patients with Stage III disease was 100% (5 of 5 patients) versus 55% for patients with Stage IV disease (27 of 49 patients; P = 0.14). For patients with Stage IV bulky nodal disease (N2c-N3), the response rate was 43% (13 of 30 patients) and the complete response rate to chemotherapy was 3% (1 of 30 patients) versus 68% (13 of 19 patients; P = 0.13) and 21% (4 of 19 patients; P = 0.07), respectively, for patients with Stage IV less than N2b disease. The local control rate after definitive therapy was 100% for patients with Stage III disease, 70% (17 of 24 patients) for patients with Stage IV less than N2b disease, and 17% (5 of 30 patients) for patients with bulky nodal disease (P = 0.0005). As of February 1991, with a median follow-up time of 38 months (range, 30 to 53 months), 4 of 5 patients with Stage III disease and 7 of 19 patients with Stage IV less than N2b disease were alive with no evidence of disease (37%) versus 0 of 30 patients with bulky nodal disease (P = 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)