Synthetic Anthracycline Shows Promise for Treatment of Small Cell Lung Cancer

Cancer Connect

According to the results of a study recently published in the Annals of Oncology, a combination of the drugs amrubicin and cisplatin shows promise for the treatment of extensive disease small cell lung cancer (ED-SCLC).

Small cell lung cancer arises from the cells within the lung. There are 3 types of small cell lung cancer: small cell carcinoma, also known as oat cell carcinoma; large cell carcinoma; and combined small cell carcinoma. At the time of diagnosis, the cancer will be defined by the extent of the disease, either as limited stage, meaning the cancer is confined to one area of the chest, or extensive stage, meaning the cancer has spread to multiple sites or distant sites. Unfortunately, in most cases small cell lung cancer is not curable, so treatments are directed toward minimizing the disease and improving the patients symptoms and quality of life. Current treatment options include surgery, radiation and chemotherapy. In contrast to non-small cell lung cancer (NSCLC), SCLC is very sensitive to a variety of chemotherapy agents including anthracyclines such as doxorubicin (Adriamycin®). However, the anthracycline group of drugs is associated with early and late cardiac damage limiting their use. Amrubicin is a totally synthetic anthracycline developed by the Japanese and is currently in phase I testing. In animal testing this synthetic agent has little if any heart toxicities.

In this recent phase I/II study, the goal was to determine the maximum tolerated doses (MTD) of the drug combination amrubicin and cisplatin and to ensure the safety of the recommended doses. Study participants were diagnosed with ED-SCLC and had not been previously treated with any type of chemotherapy. Two dose levels were designed for the study and 4 patients were enrolled in the level I dose of amrubicin 40mg/m2/day and cisplatin 60mg/m2. Three patients were enrolled at level II, which included amrubicin 45mg/m2/day and cisplatin 60mg/m2. All patients received their amrubicin doses on days 1-3 and cisplatin on day 1 only, every 3 weeks.

Results of the study indicated that both level I and II doses were safe and tolerable. The overall response rate was 87.8% among both groups. The average survival time was 13.6 months and the 1-year survival rate was 56.1%. The most common side effects that were observed included a drop in the white blood count.

Researchers concluded that the combination of amrubicin and cisplatin demonstrated a promising response rate and survival period for patients who were previously untreated for ED-SCLC. This is an important study as it shows significant activity for a totally synthetic drug, which may have been engineered to eliminate heart toxicity. Unfortunately, this drug will not be on the market for quite some time. However, Doxil® is a pegylayated liposomal form of doxorubicin that also is associated with less cardiac toxicity. Patients receiving treatment with doxorubicin or daunomycin should speak with their physician about available compounds with fewer heart-associated side effects.

Reference: Ohe Y, Negoro S, Nakagawa K, et al. Phase I-II Study of Amrubicin and Cisplatin in Previously Untreated Patients with Extensive Stage Small-Cell Lung Cancer. Annals of Oncology. 2005; 16: 430-436.

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