didimethylsulfoxide-dichloroplatinum(ii) and Carcinoma--Squamous-Cell

In order to enhance radiation effects in the treatment of unresectable Head and Neck squamous cell carcinoma, we initiated a phase I-II study in February 1991 with concomitant radiation and cisplatin in the treatment of resectable Head and Neck squamous cell carcinoma. The first patient was treated in a palliative intend for a cervical recurrence (cutaneous metastatic lymphangitis) of laryngeal cancer. The seven other patients had a Stage IV M0, previously untreated, oropharyngeal carcinoma. Standard external radiation was carried out up to a total dose of 60 Gy/6 weeks (7 MeV electron beam) for the 1st patient and 72 Gy/8 weeks (Co60 beam) for the 7 other patients. Cisplatin was given during the entire radiation treatment, by continuous infusion, 5 days a week, at doses of 4 mg/m2/d for the 1st patient, 5 mg/m2/d for the two following patients and 6 mg/m2/d for the last five patients. One patient with a poor initial performance status (three in the WHO scale) stopped his treatment on the 6th week due to a grade 3 mucositis with deglutition pneumonia. He died 2 months later with progressive carcinoma. For one other patient, treatment was discontinued for 1 week after 48 Gy, due to a grade 3 mucositis. The other patients completed the planned protocol without any interruption. Mucositis (grade 3 in two cases, grade 2 in four cases), dermitis (grade 3 in two cases, grade 2 in four cases) and neutropenia (grade 2 in two cases) were the most frequent acute toxicity. Of the seven patients treated with a curative intend, six are free of disease at 6 to 28 months after completion of treatment. A pharmacokinetic study showed a total platinum accumulation. The mean value at the end of treatment reached 1157 ng/ml. Only one patient experienced an accumulation of the ultrafilterable platinum (137 ng/ml at the end of treatment).

Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Injections, Intravenous; Male; Neoplasm Staging; Organoplatinum Compounds; Otorhinolaryngologic Neoplasms; Radiotherapy Dosage; Remission Induction

Dietary levels of beta-carotene and vitamin E have been associated with cancer prevention and to a lesser extent, with therapeutic enhancement of cancer treatment. We report on the cytotoxicity of beta-carotene, vitamin E, and the combination of beta-carotene and vitamin E in human SCC-25 squamous carcinoma cells under various environmental conditions found in solid tumor masses. Beta-Carotene was selectively cytotoxic toward normally oxygenated cells and was generally more cytotoxic at normal pH than at acidic pH (6.45). Vitamin E was selectively cytotoxic toward normally oxygenated cells following 6 h exposure at normal pH and was generally equally cytotoxic toward normally oxygenated and hypoxic cells under the other conditions tested. Beta-Carotene was an effective modulator of cisplatin (CDDP) cytotoxicity toward SCC-25 cells, whereas vitamin E was not. Both beta-carotene and vitamin E were effective modulators of melphalan cytotoxicity toward SCC-25 cells. Treatment of SCC-25 cells with beta-carotene (70 microM, 2h) resulted in a reduction in superoxide dismutase activity, in glutathione-S-transferase activity, and in nonprotein sulfhydryl levels in the cells. Exposure to vitamin E or to a combination of beta-carotene and vitamin E increased the glutathione-S-transferase activity in SCC-25 cells by 40%-45% over the control value. Treatment with beta-carotene, vitamin E, or canthaxanthin reduced the incorporation of [3H]-thymidine into SCC-25 cells but not that into normal human keratinocytes. The most marked reduction in [3H]-thymidine incorporation into SCC-25 cells occurred following treatment with the combination of beta-carotene and melphalan. We hope to continue to explore the mechanisms of this effect and to study these combinations in vivo.

Topics: Alkylating Agents; Antineoplastic Agents; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Cell Hypoxia; Cell Survival; Dose-Response Relationship, Drug; Drug Interactions; Humans; Hydrogen-Ion Concentration; Melphalan; Organoplatinum Compounds; Tumor Cells, Cultured; Vitamin E

The efficiency of the subrenal capsule assay (SRCA) was studied with fresh tissue of esophageal squamous cell carcinoma. The day-to-day changes in 10 carcinoma cases were evaluated for 9 days. The cancer cells continued to proliferate from the 3rd to the 7th day after the implantation and then decreased. The host reaction was recognized histologically from the 3rd or 4th day to the 9th day. However, the immune reaction did not significantly influence the evaluation of SRCA until the 7th day. The immunohistochemical staining with anti-bromodeoxyuridine monoclonal antibody revealed the existence of cancer cells at the DNA synthesizing stage (S stage) in the graft until the 7th day. In chemosensitivity test by SRCA, 21 patients were studied, and all were evaluable. 5-FU administration produced a response in 8/21 cases (38.1%), VDS in 8/21 (38.1%), and CDDP in 3/21 (14.3%). Used in combination, CDDP + VDS was effective in 7/18 cases (38.9%) and CDDP + BLM in 6/18 cases (33.3%).

Topics: Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cell Division; Esophageal Neoplasms; Female; Fluorouracil; Humans; Immunohistochemistry; Mice; Middle Aged; Neoplasm Transplantation; Organoplatinum Compounds; Peplomycin; Subrenal Capsule Assay; Time Factors; Vindesine

Hearing ability was examined in patients with head and neck cancer treated by combined CDDP and electron beam therapy. In 3 of 7 patients with maxillary cancer, hearing impairment apparently attributable to the therapy was noted on the affected side. In one of these 3 patients, the temporal bone was observed, but the cause of hearing impairment could not be determined. We present patients with cancer of the external ear in whom radiation-caused hearing impairment worsened probably due to combined CDDP and electron beam therapy.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Combined Modality Therapy; Ear, Inner; Female; Hearing Disorders; Humans; Male; Maxillary Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Radiotherapy; Temporal Bone

A case of carcinoma of the tongue treated with neoadjuvant chemotherapy has been reported. The patient was a 61-year-old man complaining of tumor and contact pain at the left margin of the tongue. The tumor was oval and elastic soft with pedicle, measuring 26 X 16 X 8 mm in size. The tumor was histopathologically diagnosed as a highly differentiated squamous cell carcinoma. The patient was treated with CDDP (75 mg/body) and PEP (5 mg/body) for 5 days. After two trials with about a 3-week interval, treatment result showed partial response. This result demonstrated that combination chemotherapy of CDDP and PEP is an effective regimen for remission neoadjuvant chemotherapy in patients with squamous cell carcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Humans; Male; Middle Aged; Organoplatinum Compounds; Tongue Neoplasms

As one method of multidisciplinary treatment for cancer of the uterine cervix, a combination IAC using CDDP and 5-FU was applied. Six operable and three inoperable, advanced patients were treated with a single 100-120 mg/body IAC bolus of CDDP followed by a continuous IA infusion of 2,500 mg/body of 5-FU. This was combined with surgical therapy in the former group and radiotherapy in the latter group. In operable cases, the extirpated tissues were examined histopathologically for effects of the combination IAC. Microscopic findings included atrophy and swelling of the cancer cell nucleus, plus variable diffused reduction of the cancer cell nest accompanied by vacuolation of the cytoplasm. In inoperable cases, observations carried out by graphical scintigram, and clinical investigation at 10 days after the IAC, indicated improved conditions. Among the adverse reactions, renal dysfunction recovered two weeks after IAC. No evidence of severe myelosuppression was observed. Therefore, IAC with CDDP and 5-FU, plus surgery or radiotherapy, against carcinoma of the cervix had favorable laboratory and clinical results.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Kidney; Middle Aged; Organoplatinum Compounds; Uterine Cervical Neoplasms