Topics:

Asian Study Suggests Combination of Docetaxel/Capecitabine Active in Chemonaive Patients With Advanced Non–Small-Cell Lung Cancer

Asian Study Suggests Combination of Docetaxel/Capecitabine Active in Chemonaive Patients With Advanced Non–Small-Cell Lung Cancer

GOYANG, Korea-Docetaxel (Taxotere) and capecitabine (Xeloda) combination therapy is active in chemonaive patients with advanced non-smallcell lung cancer (NSCLC). The regimen, however, was frequently associated with significant nonhematologic toxicities, suggesting a clinical synergism in terms of both efficacy and toxicity. Ji-Youn Han, MD, PhD, Center for Lung Cancer, National Cancer Center, Goyang, Korea, reported these findings (ASCO abstract 2691). "Cisplatin-based chemotherapy is currently considered the standard treatment for advanced NSCLC. However, cisplatin causes considerable toxicities, which has generated interest in identifying a chemotherapy regimen that is less toxic," Dr. Han said in explaining the rationale for conducting the phase II study. "Recently, a number of combinations of new agents active in NSCLC were introduced and they yield a better efficacy-toxicity ratio." Capecitabine is an oral fluoropyrimidine carbamate, which was rationally designed to generate fluorouracil (5-FU) preferentially in tumor tissue by thymidine phosphorylase (TP). High expression of TP is frequently observed in many malignancies including NSCLC. "Although the antitumor activity of capecitabine has not been evaluated in NSCLC, the relatively high expression of TP in NSCLC provides a rationale for the use of capecitabine in NSCLC patients," Dr. Han said. Synergistic Interaction "Furthermore, preclinical studies of human breast and colon cancer xenograft models demonstrated that docetaxel was more active in combination with capecitabine than with 5-FU or UFT (uracil and tegafur). This in vivo synergistic activity was dependent on docetaxel-induced upregulation of TP." Recently a phase III study demonstrated that capecitabine/docetaxel combination therapy was more effective than single-agent docetaxel in anthracyclinepretreated patients with advanced breast cancer. The significantly superior time to progression and median survival was achieved with the addition of capecitabine to docetaxel; however, toxicity was considerable. "The more favorable toxicity profile of weekly docetaxel and the time-dependent character of docetaxel-mediated upregulation of TP provide the rationale for the combination of weekly docetaxel and capecitabine," Dr. Han noted. She added that the results of the phase I study of a weekly docetaxel and capecitabine combination in patients with advanced NSCLC "provide additional supporting data of a synergistic interaction between docetaxel and capecitabine." No Complete Responses Patient eligibility for the study required stage IIIB or IV NSCLC, bidimensionally measurable disease and Eastern Cooperative Oncology Group (ECOG) performance status 2. Patients could have no prior chemotherapy or radiation therapy, unless the irradiated area was not the only source of measurable disease; an estimated life expectancy of at least 12 weeks; and adequate hematologic function. Treatment consisted of docetaxel 36 mg/m2 IV on day 1 and 8 plus capecitabine 1,000 mg/m2 po bid on days 1 to 14 of a 21-day cycle, for a maximum of six cycles. Premedication with oral dexamethasone 8 mg was given 12 hours before and again immediately before docetaxel, as well as 12 hours after docetaxel. Of 39 patients enrolled, all were evaluated for toxicity and 36 for response. Overall response rate was 53%, including 19 partial responses, but no complete response. Median duration of response was 6.2 months (range 2.1-12.4 months). At follow-up (median of 10.3 months), 13 patients died. The estimated 1-year survival rate was 61%, and there were two treatment-related deaths, one pneumonia and one sepsis. Hematologic toxicity was mild to moderate, although grade 3/4 neutropenia occurred in 13% of patients. Grade 2/3 nonhematologic toxicities were frequent, including asthenia (51%), stomatitis (33%), hand-foot syndrome (33%), and diarrhea (29%). "This regimen is attractive because of its relatively high response rate and its convenient outpatient administration," Dr. Han said. "However, it was frequently associated with moderate to severe nonhematologic toxicities, suggesting clinical synergism in terms of not only efficacy, but also of toxicity. Further adjustment of the dose-schedule is recommended to maximize the therapeutic index of this regimen in chemonaive advanced NSCLC patients."

 
Loading comments...

By clicking Accept, you agree to become a member of the UBM Medica Community.