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.