Automated Toxaphene Quantitation by GC/MS.

Toxaphene is a complex mixture of at least 600 hexa- to decachlorinated bornanes and bornenes, which was used as an insecticide from the late 1950s to the early 1980s. Like PCBs and other environmentally persistent organochlorine pesticides, toxaphene is ubiquitous in the environment. Toxaphene's complex composition makes its accurate quantitation difficult. We report here an automatic, gas chromatographic mass spectrometry method (using electron capture negative ionization) that is precise and fast. This method is implemented by a small QBasic program that compares peak area ratios to the predicted chlorine isotopic ion ratios. This method decreases the time required for analysis while maintaining precise quantitation. The method is verified with standard and unknown samples contaminated with various amounts of other organochlorine pesticide interferents.

Observations on control of N2 and N3 neck disease in squamous cell carcinoma of the head and neck by intra-arterial chemoradiation.

Patients with head and neck squamous cell cancer with N2 and N3 neck disease have a poor prognosis and are at risk to fail regionally despite combined surgery and radiation. Twenty-two patients with N2 and N3 neck disease (and T3-4 primaries) were treated with intra-arterial, high-dose cisplatin (CDDP), 150 mg/m2 per week for 4 weeks, and concurrent radiation. All patients were followed for at least 2 years or until death from any cause. Twenty patients had a complete response at the primary site. Two of the 20 with a complete response later had a neck recurrence and died. Five patients with palpable nodes after treatment underwent fine-needle aspiration (FNA), one of which was positive and two suggestive of cancer. Six neck dissections were performed in this group, only two of which had positive nodes. This chemoradiation protocol may offer reasonable control of N2 and N3 neck disease in advanced head and neck squamous cell cancer. Neck dissection appeared to be necessary in only those patients with nodes 8 weeks after treatment in whom FNA was positive or suggestive of cancer. Because of the relatively small size of this series, additional accrual and monitoring of such patients is planned.

Phase I trial of retinoic acid and cis-platinum for advanced squamous cell cancer of the head and neck based on experimental evidence of drug synergism.

OBJECTIVE: Cis-platinum and 13-cis-retinoic acid have received much attention in the treatment of head and neck squamous cell cancer. Even though they have different mechanisms of action, little information is available on their interaction. This paper reviews experimental evidence for retinoic acid-cis-platinum synergy and presents toxicity data from patients with stage IV head and neck squamous cell cancer participating in a phase I trial combining 13-cis-retinoic acid and cis-platinum. METHODS: Patients were given 13-cis-retinoic acid orally daily for 7 days before and daily during high-dose (150 mg/m2 per week for 4 weeks) intraarterial cis-platinum treatment with concurrent radiation. Toxicity was scored with use of the cancer and leukemia group B scale. RESULTS: In the phase I clinical trial, 15 patients were treated to determine a maximum tolerated dosage for 13-cis-retinoic acid of 20 mg/day. Grade 4 hematologic toxicity was dose limiting in 3 of 8 patients treated with 40 mg/day and in 1 patient treated with 60 mg/day. There were no deaths caused by toxicity; 12 of the 15 patients received all four weekly doses and the remaining 3 received three doses. Of 10 patients with fully evaluable data, all achieved a complete response at the primary site and 9 had a complete response in the neck. One patient had persistent neck disease after chemoradiation, and this tumor was removed with neck dissection. CONCLUSIONS: 13-Cis-retinoic acid and cis-platinum are strongly synergistic against head and neck squamous cell cancer in vitro. Pretreatment with retinoic acid results in stronger synergy than concurrent drug exposure alone. Preliminary clinical experience with combined retinoic acid and cis-platinum in a design that parallels the in vitro study indicates that toxicity is acceptable with 13-cis-retinoic acid dosages of 20 mg/day in a high-dose-intensity intraarterial chemoradiation regimen.