Paclitaxel and gemcitabine vs. carboplatin and gemcitabine. A multicenter, phase III randomized trial in patients with advanced inoperable non-small cell lung cancer (NSCLC)
Reviewer: S. Jack Wei, MD
University of Pennsylvania School of Medicine
Last Modified: May 14, 2005
Presenter: P.A. Kosmidis
Presenter's Affiliation: Hellenic Cooperative Oncology Group
Type of Session: Scientific
- Early phase data has shown the combination of paclitaxel and gemcitabine may be as active and well tolerate as the combination of carboplatin and gemcitabine in patients with inoperable and advanced NSCLC
- This trial was designed to compare the two combinations of chemotherapy and evaluate for a survival difference between the two.
Materials and Methods
- Patients with histologically proven inoperable, recurrent, or metastatic stage IIIB (wet) or stage IV NSCLC were randomized to:
- 1) P+G: Paclitaxel (200 mg/m2 d1) + gemcitabine (1000 mg/m2 d1-8) q21 days x 6 cycles
- 2) Cb+G: Carboplatin (AUC=6 d1) + gemcitabine (1000 mg/m2 d1-8) q21 days x 6 cycles
- Eligibility requirements included ECOG performance status 0 or 1, stable brain metastasis, measurable disease outside of radiotherapy port unless progression was previously documented, and adequate bone marrow, hepatic, and renal function.
- Primary endpoint was overall survival (OS) with secondary endpoints of response rate, time to disease progression, and toxicity.
- From 10/00 to 3/04, 512 patients were randomized with 445 patients analyzed.
- The two patients groups were well balanced with regards to age, gender, performance status, stage, prior radiotherapy, prior lung surgery, histology, and number of metastatic sites.
- The majority of patients on both arms <3 sites of metastatic disease.
- There was no difference between to two groups with regards to rates of lymph node involvement, pleural involvement, liver metastases, bone metastasis, brain metastasis, and adrenal gland metastasis.
- There was no difference with regards to the dose of gemcitabine delivered between the two groups with adequate rates of delivery of both the paclitaxel and the carboplatin.
- There was no difference in overall response rates: P+G=31% vs Cb+G=28.5% (p=0.47).
- Median time to disease progression was 5 mo for both arms.
- There was no difference in median survival: P+G=10 mo. vs. Cb+G=10.5 mo.
- There was a higher rate of hematologic toxicity in the Cb+G arm but a higher rate of alopecia and neurotoxicity in the P+G arm.
- Male patients, patients who had not had prior lung surgery, patients who had performance status of 1, and patients with systemic symptoms had a poorer survival.
- Patients with non-squamous cell histology, adrenal or bone metastases, and >=3 sites of metastatic disease also had a poorer survival.
- There was no difference between the two treatments with regards to response rates, median survival, 1-year survival, 2-year survival, and time to progression.
- Cb+G results in higher rates of hematologic toxicity while P+G results in higher rates of alopecia and neurotoxicity.
- Previously noted predictors of poor outcome such as male gender, performance status, systemic systems, and higher number of metastatic sites were confirmed
The results of this trial show that the use of a non-platinum containing doublet results in similar outcomes as a platinum-containing doublet. Although this study was designed to find an overall survival benefit to the use of P+G compared to Cb+G, the results are more consist with that of an equivalence study. The standard treatment for this group of patients has been the use of a platinum-based drug in combination with a second chemotherapeutic agent. The results of this study would seem to indicate that the use of two non-platinum containing drugs may results in similar outcomes with different, but equivalent rates of toxicity. Currently, the standard chemotherapy in these patients remains a platinum-containing doublet; however, it may be reasonable to treatment with a non-platinum-based doublet. Alternative therapies including targeted therapies are needed to improve the overall poor outcomes in these patients.