Docetaxel and irinotecan, alone and in combination, in the treatment of non-small cell lung cancer

Single-agent activity has been observed for both docetaxel and irinotecan in several solid tumors, including non-small cell lung cancer (NSCLC). Compilation of data from phase II trials of single-agent docetaxel therapy in NSCLC yielded overall response rates of 26% and a 1-year survival rate of 52%. Furthermore, a recent study that combined radiotherapy with concurrent docetaxel treatment reported an overall response rate of 77%. The most important adverse effect of docetaxel therapy is neutropenia. Phase II trials of single-agent irinotecan for NSCLC patients resulted in response rates of 15% to 31%. The main toxicities were neutropenia and diarrhea. Investigators have begun to explore the efficacy of combining docetaxel and irinotecan. The results of preclinical studies suggest that schedule and order of administration may be important. A Japanese study evaluated the combination in previously untreated patients with NSCLC, and found eight partial responses in 26 patients (32%). A recent phase I study at the Mayo Clinic showed partial responses in three of five patients who received irinotecan followed by docetaxel. In a phase I study conducted at Yale Cancer Center, escalating doses of docetaxel (25 to 40 mg/m²) were given before irinotecan (50 mg/m²) for 4 weeks followed by a 2-week rest. There was one partial response among five evaluable patients with NSCLC (one of four among patients who had received no prior chemotherapy). The results of these studies suggest that the combination of docetaxel and irinotecan shows promise in the treatment of NSCLC. Irinotecan also has been used in combination with other chemotherapeutic agents. The irinotecan/etoposide combination has been less extensively evaluated but thus far appears to be associated with considerable toxicity, particularly myelosuppression, without clear therapeutic advantage. One report of the use of the triple combination of irinotecan/cisplatin/etoposide resulted in 16 partial responses in 42 NSCLC patients (38%). Like docetaxel, irinotecan has been used effectively in conjunction with radiation therapy, with partial response rates in some studies of more than 70%.