High-dose cisplatin and vinblastine infusion with or without radiation therapy in patients with advanced non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) patients with locally advanced or metastatic measurable disease were given a combination of cisplatin, 200 mg/m2 divided in five daily doses, and simultaneously, vinblastine, 7.5 mg/m2 as a continuous intravenous (IV) infusion over five days. Five courses of chemotherapy were planned. Afterwards or on progression, patients were randomized to receive maximally tolerated radiation to all sites of disease v observation only. Forty males and seven females were entered. Median age was 60 years (range, 37 to 74), median Karnofsky performance status was 70 (range, 30 to 90). Five patients had previous brain radiation therapy for metastatic disease, all others were previously untreated. Side effects in the 87 courses of chemotherapy administered included leukopenia (WBC less than 1,000/microL following nine courses) and thrombocytopenia (platelets less than 20,000/microL following four courses). Ten patients became septic, nine of them while leukopenic. Elevations of serum creatinine followed eight courses; in all cases the level was less than 3.0 mg/dL. Nausea and vomiting were mild to moderate. Five patients experienced mild hypoacusis and six had sensory polyneuropathy. The deaths of three patients were considered drug-related. The response rate was 28%. The median survival for the group was 22 weeks, 63.2 weeks for responders and 17.9 weeks for nonresponders. Twenty-six patients received radiation therapy, 16 randomized to this arm as planned, ten to palliate symptoms. Median survival of all irradiated patients was 24.8 weeks. Seven responders to chemotherapy were randomized to receive radiotherapy; their median survival was 25 weeks. In six responders randomized not to receive radiation, the median survival was 77.8 weeks (P greater than .3). Among nonresponding patients, the median survival of those radiated was 22.2 weeks, while that of nonradiated patients was 11 weeks. This regimen is cumbersome and toxic. It has offered no major survival benefits, or improvement in response rates, therefore, we do not recommend it for the standard treatment of NSCLC.

Approaches to ablating the myelotoxicity of chemotherapy.

Myelotoxicity remains a significant dose-limiting side effect of chemotherapy contributing to the morbidity and mortality of patients undergoing treatment for cancer. A number of different experimental approaches are being studied, both in the clinic and in the laboratory, in an attempt to prevent this iatrogenic complication. The present review provides a synopsis of the various myeloprotective strategies now being employed in experimental trials. Emphasis is placed on the use of putative physiologic bioregulatory molecules (lactoferrin, prostaglandin E, interferon) to prevent or lessen chemotherapy-induced myelotoxicity, with consideration also given to other promising treatment modalities (i.e., adenosine, lithium, diethyldithiocarbanate).

Diagnostic significance of levamisole-resistant alkaline phosphatase in cytochemistry and immunocytochemistry.

The authors have used two immunoalkaline phosphatase methods to study nonhematopoietic tumor tissues of four patients, one each with alveolar cell carcinoma of the lung, renal cell carcinoma, gastric adenocarcinoma, and colon carcinoma. They found, regardless of specific antibodies used, definite enzyme activity in the tumor cells of these four patients. Although it was possible to determine that the tumor cells were epithelial in origin because of their intense staining with antibodies to epithelial cell antigens, control slides labeled with nonimmune mouse ascites also contained cells with definite enzyme activity. In two of these cases, unlabeled smears were stained for alkaline phosphatase and showed that the tumor cells contained endogenous levamisole-resistant enzyme activity. This endogenous enzyme activity is not demonstrable in either the benign cells of these cases or the benign or malignant cells of other control cases. The findings suggest that the immunoalkaline phosphatase methods also have their inherent endogenous enzymic problems. They also suggest that cytochemical demonstration of levamisole-resistant alkaline phosphatase may be a useful cell marker for the identification of tumor cells in serous effusions.

A phase II trial of vinblastine, bleomycin, and cisplatin induction followed by dacarbazine and dibromodulcitol maintenance in the treatment of metastatic melanoma. A follow-up study of twenty-two patients.

Twenty-two patients with metastatic melanoma were treated with a chemotherapy regimen consisting of two cycles of induction therapy with vinblastine, bleomycin, and cisplatin, followed by maintenance therapy with dacarbazine and dibromodulcitol. A 17% response rate was noted in this patient group, with a median survival of 40 weeks. Objective responses were limited to cutaneous, nodal, pulmonary, and one adrenal site of metastatic disease. Toxicity was acceptable and was limited to myelosuppression and nausea with emesis. Further study appears warranted to define the optimal treatment plan for metastatic melanoma.

A phase II trial of chlorambucil in non-small cell lung cancer.

A Phase II trial of high-dose chlorambucil at 108 mg/m2 was undertaken in non-small cell lung cancer. No complete or partial objective responses were observed, and significant toxicity, including nausea, vomiting, and seizures, was noted. Chlorambucil at this dose and schedule of administration is not recommended for the treatment of non-small cell lung cancer.

A phase I trial of chlorambucil administered in short pulses in patients with advanced malignancies.

We carried out a phase I trial with chlorambucil. Thirty patients with advanced cancer were entered in six dose levels: 36, 48, 60, 84, 108, and 144 mg/m2. The drug was given in six divided oral doses every 6 hours and the regimen was repeated every 3 weeks. The median age was 62 years (31-84), median Karnofsky performance status (KPS) 60 (40-90). All patients but one had received prior radiation therapy, chemotherapy, or both. Central nervous system toxicity was dose limiting, occurring in 5 of 6 patients at 144 mg/m2. It was characterized by transient seizures, hallucinations, lethargy, stupor, and coma. Metoclopramide was successful in controlling nausea and vomiting, which was severe if the antiemetic was not used. Leukopenia (3 patients) and thrombocytopenia (2 patients) were mild. One patient with colorectal carcinoma had a minor response, and two patients with non-small cell lung cancer had stable disease. A safe dose for phase II trials is 108 mg/m2 in six 6-hourly oral doses.