Phase II Study of First-Line Sequential Chemotherapy with Gemcitabine-Carboplatin Followed by Docetaxel in Patients with Advanced Non-Small Cell Lung Cancer

Abstract

Rationale: Despite the use of novel chemotherapeutic agents, patients with advanced non-small cell lung cancer (NSCLC) continue to show a poor survival. Objectives: To assess the safety and efficacy of a novel sequential and putatively non-cross-resistant chemotherapy regimen. Methods: Eligibility included: stages IV and IIIB (malignant pleural effusion), performance status 0–1, and adequate renal, hepatic and bone marrow function. Patients with previously treated and controlled brain metastases were not excluded. Responses were determined according to the Response Evaluation Criteria in Solid Tumors. Treatment consisted of gemcitabine, 1,000 mg/m², on days 1 and 8, and carboplatin, AUC = 5, on day 1 every 4 weeks (2–4 cycles) followed by docetaxel, 75 mg/m², on day 1 every 3 weeks (4 cycles). Docetaxel was given after four cycles of gemcitabine-carboplatin or if progression of disease occurred, after the first two cycles. Results: Forty patients were enrolled. All patients received at least one cycle of gemcitabine-carboplatin. Due to PD, 15 patients received fewer than four cycles and only 1 received docetaxel subsequently. Of the 25 patients who completed four cycles of gemcitabine-carboplatin, 23 received docetaxel.In total, 24 patients received at least one cycle of docetaxel, and 12 patients completed four cycles of both regimens. The overall response rate was 23.6% (9/38 patients, 95% confidence interval, CI, 11–40%), with 15.8% (6/38 patients, 95% CI, 6–31%) and 12.5% (3/24 patients, 95% CI, 3–32%) response rates to gemcitabine-carboplatin and docetaxel, respectively. No patient with PD on gemcitabine-carboplatin responded to docetaxel. Toxicities were tolerable and mostly hematologic. Median survival time and progression-free survival were 6.7 and 4.9 months, respectively, with a 1-year survival of 37.5%. Conclusion: Sequential gemcitabine-carboplatin and docetaxel can be safely administered in advanced NSCLC. Our results are comparable to those achieved with other similar regimens and do not represent a significant improvement in the treatment of advanced NSCLC.

Individualized therapy in non-small-cell lung cancer: future versus current clinical practice

“…Patients achieved an RR of 44% and the 1-year OS and PFS rates were 59% (median, 13.3 months) and 14% (median, 6.6 months), respectively. The results from this study compared favorably with those of another phase II study of uncustomized treatment in similar patient populations (RR, 24%; median OS, 6.7 months) (Chiappori et al, 2005). Collectively, these data suggest that the identification of patients with low expressions of ERCC1 and RRM1 allows for a strategy of individualized chemotherapy in this population, which may result in an improved outcome (Huang et al, 2006;Simon et al, 2007).…”

Pharmacogenomics: A reality or still a promise?

“…This was found to be the case, with data indicating an unprecedented 12-month survival rate of 62%. Comparison with another study (MCC-12621) conducted at the same institution by the same physicians and with matching referral patterns, staging and enrolment criteria revealed that results obtained in the MADeIT study were close to 50% better (Table 1) [40]. Similarly, results from another study (E1594) revealed that the tailored treatment used in the MADeIT trial produced 12-month survival values that were almost double those previously observed [22].…”

Triplet Platinum-based Combination Sequential Chemotherapy Improves Survival Outcome and Quality of Life of Advanced Non-small Cell Lung Cancer Patients

“…When sequential chemotherapy offered, it is possible to overcome the drug resistance of single regimen used for a relatively longer period. Actually, the debate about maintenance therapy for advanced NSCLC had been re-ignited in recent years (Hosoe et al, 2003;Grossi et al, 2004;Chiappori et al, 2005;Pallis et al, 2006). The results of several randomized phase III studies reported showing a significant advantage of maintenance treatment in advanced NSCLC (Ciuleanu et al, 2007;Fidias et al, 2009;Cappuzzo et al, 2010).…”