A Phase I study of chronic daily dosing of oral etoposide in combination with cisplatin for patients with advanced cancer

Article Abstract:

Etoposide is effective against a variety of human cancers. Unlike like some chemotherapeutic agents which directly act on the genetic material inside the cell, etoposide seems to damage DNA indirectly by affecting an enzyme within the nucleus, DNA topoisomerase II. The interaction between the drug and the enzyme is reversible, and when the drug administration is stopped the topoisomerase II activity begins to return to normal. The mechanism of action of etoposide makes the effectiveness of the drug strongly dependent upon the schedule of administration. Usually, without prolonged exposure the cancer cells treated with etoposide will recover from the toxic effects rather than die. Since etoposide appears to act synergistically with the anticancer drug cisplatin, a study was undertaken to evaluate a schedule of treatment with these two drugs for 22 patients with advanced lung cancer. Eighteen patients had primary lung cancer and four had metastatic cancer in the lungs which had spread from cancer originating elsewhere in the body. The treatment consisted of intravenous cisplatin and oral etoposide on the first day of a course of treatment; the course then continued with oral etoposide every day for 21 days. After 21 days, the etoposide was discontinued for one week prior before the start of the next course. Five different dose levels were evaluated, ranging from 80 to 100 milligrams of cisplatin per square meter of body area and from 20 to 50 milligrams per day etoposide per square meter of body area. Hair loss was a common side effect, and most patients experienced nausea and vomiting that was not so severe that it could not be controlled with antiemetic drugs. Four patients achieved partial responses, which ranged from 1.3 months to over 5.8 months. The study found that an 80 milligram dose of cisplatin on day one and a 40 milligram dose of etoposide daily for 21 days, per square meter of body area, would be a reasonable starting point for further evaluation of the treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

Antineoplastic agents, Cisplatin, Etoposide

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A comparative trial of LC9018 plus doxorubicin and doxorubicin alone for the treatment of malignant pleural effusion secondary to lung cancer

Article Abstract:

The pleura is a thin tissue that covers the lungs and lines the cavities that contain the lungs. Some diseases result in the effusion of fluid into the pleural cavity between the lung and the chest wall. This fluid impairs breathing and can significantly shorten the life of a seriously ill patient. Such malignant pleural effusion is a common complication of lung cancer. Draining the fluid is the first step, and treatment is generally given to prevent the further accumulation of fluid. Bacteria often have dramatic effects on many aspects of bodily function; substances called biologic response modifiers may be prepared from such bacteria. One such biologic response modifier, LC9018, is obtained from the bacteria Lactobacillus casei and appears to be useful treating malignant pleural effusion. Ninety-five lung cancer patients with malignant pleural effusion were randomly assigned to receive an infusion directly into the pleural cavity of either the chemotherapeutic agent doxorubicin alone or a combination of doxorubicin and LC9018. The effects of treatment could be evaluated in 76 patients. There was a response rate of 74 percent for the patients treated with the combination of LC9018 and doxorubicin. The response rate was only 40 percent for the patients treated with doxorubicin alone. This significant difference was reflected in the patients' performance status and improvement of chest pain and other symptoms. The bacterial product LC9018 did cause some fever among the patients and some limited abnormal liver function, but these effects were not serious. These studies indicate that LC9018 should be included in the treatment of malignant pleural infusions. (Consumer Summary produced by Reliance Medical Information, Inc.)

Care and treatment, Complications and side effects, Lung cancer, Pleural effusions, Pleural effusion

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Combination chemotherapy with or without radiation therapy in small cell lung cancer: an analysis of a 5-year follow-up

Article Abstract:

Small cell lung cancer (SCLC) grows rapidly and has a high propensity for spreading quickly and widely. Although SCLC is sensitive to both radiation and chemotherapy, most patients suffer relapses within a year or two, probably due to the emergence of subpopulations of cancer cells resistant to chemotherapy. Since some anecdotal evidence suggested that doxorubicin played a role in the health of the few patients who survived SCLC more than five years, a retrospective study was completed of 159 patients with SCLC. Ten patients survived for five years or more; this indicates a five-year survival rate of 6.3 percent, and a cure rate comparable to other published reports. The nine patients who could be evaluated had a complete response to initial chemotherapy. Statistical analysis of the data did not reveal a significant role for radiotherapy. In the patients studied, age and sex did not appreciably affect survival. These results are not in agreement with some other published data. Chemotherapeutic regimens containing doxorubicin were, however, significantly correlated with improved chances of survival. These results indicate that doxorubicin is an indispensable part of combination anticancer therapy for small cell lung cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)

Radiotherapy, Chemotherapy, Lung cancer, Small cell, Small cell lung cancer

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