[Show abstract][Hide abstract] ABSTRACT: Patients with resectable stage IIIA-N2 non-small cell lung cancer should receive induction chemotherapy before surgery. The aim is to early control systemic disease, eventually cure the mediastinal tumor spread and improve patients' survival. A recent metanalysis of randomized trials with second-generation platinum-based combinations has reinforced the evidence concerning the benefit of induction chemotherapy followed by surgery versus surgery alone in resectable disease. Moreover a large number of phase II trials have explored the activity and feasibility of platinum-based combinations with third-generation drugs in the same setting. Still opened questions to address with current clinical research are the eventual role of radiotherapy as induction treatment, the impact of definite chemoradiation versus induction treatment followed by surgical resection on local control and survival and finally the non-easy choice between neo-adjuvant and adjuvant chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: The objectives of this phase I/II study were to define the maximum tolerated dose (MTD), safety, and activity of cisplatin, etoposide, and gemcitabine (PEG) in the treatment of previously untreated patients with small-cell lung cancer (SCLC).
Chemonaive patients received fixed doses of gemcitabine (1000 mg/m(2) on days 1 and 8) and cisplatin (70 mg/m(2) on day 2) and escalating doses of etoposide (starting dose of 50 mg/m(2) on days 3, 4, and 5) every 3 weeks. No prophylactic granulocyte colony-stimulating factors were used.
From September 1998 to April 2000, 56 patients with limited- or extensive-stage SCLC were enrolled and received a total of 235 cycles. Two different etoposide doses were tested in eight patients. At the second level (75 mg/m(2)), two out of two patients experienced dose-limiting toxicities (neutropenia and thrombocytopenia) and no further dose-escalation was attempted, thus an etoposide dose of 50 mg/m(2) was defined as the MTD. In the subsequent phase II evaluation, 48 additional patients were enrolled, for a total of 54 patients treated at the MTD. Grade 3/4 neutropenia and thrombocytopenia occurred in 66.7 and 53.7% of patients, respectively. Non-hematologic toxicity was mild, with grade 3 diarrhea and fatigue as the main side effects. Two patients died of neutropenic sepsis (one at 75 mg/m(2) and the other at 50 mg/m(2) etoposide). Ten complete and 29 partial responses were reported, for an overall response rate of 72.2% (95% confidence interval, 56.6-85.0%). The median duration of response and median survival were 8.0 and 10 months, respectively, with a 1-year survival probability of 37.5%.
The combination of PEG is feasible and well tolerated as front-line chemotherapy in SCLC. A randomized comparison of this triplet is underway.
Lung Cancer 04/2003; 39(3):331-8. DOI:10.1016/S0169-5002(02)00500-7 · 3.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore a new schedule of gemcitabine-cisplatin (GP) combination therapy using two different cisplatin doses in patients with advanced non-small-cell lung cancer (NSCLC).
From May to December 1997, 92 chemonaive patients entered the study and 88 (28 with locally advanced and 60 with disseminated NSCLC) were evaluable for response and toxicity (45 in arm A and 43 in arm B). Patients were randomly assigned to arm A or arm B. Gemcitabine 1000 mg/m2 was given on days 1-8 plus cisplatin 100 mg/m2 in arm A and cisplatin 70 mg/m2 in arm B on day 2 of every 21-day cycle.
The overall response rates in arms A and B were 42% (95% confidence interval (CI): 27.8%-56.7%) and 47% (95% CI: 31.6%-61.5%), respectively. Median duration of response was 9.7 months (range 1.8 to 30.9 months; 13.1 and 9.5 months for arm A and B, respectively), and median survival was 12 months (range 0.2 to 31.1 months; 15.4 and 11.5 months for arm A and B, respectively). Major WHO grade 3-4 toxicities in arm A vs. arm B included: thrombocytopenia (23% vs. 17% of courses), leukopenia (15%, vs. 4% of courses), anemia (7% vs. 6% of courses), and nausea-vomiting (20% vs. 7% of patients). Grade 1-2 nephrotoxicity occurred in 20% of patients in arm A and in 7% of patients in arm B, with one grade 4 episode in arm A. Six patients discontinued treatment because of toxicities, 5 in arm A and I in arm B.
Results of this trial indicate that both schedules are feasible and active, with a milder toxicity in the arm with the lower cisplatin dose.
Annals of Oncology 11/2000; 11(10):1295-300. DOI:10.1023/A:1008334610955 · 7.04 Impact Factor