Etoposide phosphate or etoposide with cisplatin in the treatment of small cell lung cancer: randomized phase II trial.
Etoposide phosphate, a water soluble prodrug of etoposide, has several potential advantages including easier and more rapid administration, avoidance of large fluid loads, and elimination of hypersensitivity reactions and other problems related to the solubilizer. This randomized Phase II study was done to evaluate the efficacy and toxicity of etoposide phosphate and etoposide, when used in combination with cisplatin in the treatment of patients with small cell lung cancer. Previously untreated small cell lung cancer patients were randomized to receive cisplatin in combination with molar equivalent does of either etoposide or etoposide phosphate. The patients were evaluated with respect to response rate, time to progression, survival, and toxicity. Response rates with etoposide phosphate and etoposide were 61% (95% confidence interval 55-67%) and 58% (95% confidence interval 52-64%), respectively (P = 0.85). Median time to progression was 6.9 months for patients who received etoposide phosphate and 7.0 months for those with etoposide (P = 0.50). For extensive stage disease patients, median survival with etoposide phosphate was 9.5 months versus 10 months for etoposide (P = 0.93). The corresponding median survivals for patients with limited stage disease were > 16 months and 17 months, respectively (P = 0.62). Myelosuppression was the most common toxicity; Grade 3 and 4 leukopenia occurred in 63% of patients receiving etoposide phosphate compared with 77% receiving etoposide (P = 0.16). The combination of etoposide phosphate and cisplatin is effective in the treatment of small cell lung cancer, and can be administered with acceptable toxicity. This study was not designed to be a formal Phase III comparative trial, but the efficacy and toxicity observed with this regimen were found to be similar to a standard etoposide/cisplatin regimen, using molar equivalent etoposide doses. Etoposide phosphate is preferable to etoposide because it is easier to use.
Greco
F A
FA
Sarah Cannon-Minnie Pearl-Cancer Center, Nashville, TN 37203, USA.
Hainsworth
J D
JD
D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity*; D016190:Carboplatin / Q000008:administration & dosage / Q000633:toxicity; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D005047:Etoposide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009943:Organophosphorus Compounds / Q000627:therapeutic use* / Q000633:toxicity*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; C061400:etoposide phosphate; D005047:Etoposide; D016190:Carboplatin