Early Tandem High-Dose Ifosfamide, Carboplatin, Etoposide Therapy with Stem Cell Rescue for Small-Cell Lung Cancer: Brief Report on the Results of a Phase-I/II Trial

Abstract

Objective: High-dose therapy (HDT) for small-cell lung cancer is experimental. Late intensification HDT for chemosensitive disease can increase the number and quality of remissions and prolong relapse-free survival, but has not yet shown impact on overall survival. This is possibly due to resistant residual disease. To overcome the development of resistance, we have tested early intensification tandem HDT. Methods: We performed a phase-I/II trial using 1 conventional cycle of ifosfamide, carboplatin, etoposide (ICE) plus granulocyte colony-stimulating factor for stem cell recruitment followed by 2 cycles of high-dose ICE with rescue by CD34+ cell-enriched peripheral blood mononuclear cells. Dose escalation was performed for the 2 high-dose ICE cycles. Radiotherapy for limited disease was according to standard protocols. Results: 17 patients were entered: 2 female patients; 15 male patients; median age 53 (range 36–65) years; 2 patients with limited disease, and 15 patients with extensive disease. We treated 4 patients at dose level 1, 11 patients at level 2, and 2 patients at level 3. The maximum tolerable dose was at level 2 with neuropathy being dose-limiting. Overall, toxicity was ≤grade 2 for all patients up to dose level 2 with hematotoxicity being grade 4 for all patients. There were 15 partial remissions (88%), 1 no change (6%), and 1 progressive disease (6%). Median time to progression was 7.9 months. Overall survival was 12.9 months (median). Conclusions: Early intensification with this protocol is feasible. Although a comparatively good response rate and median time to progression have been observed in this group dominated by patients with extensive disease, overall survival is short and no substantial long-term survival was found.

Standard versus Dose-Intensified Chemotherapy with Sequential Reinfusion of Hematopoietic Progenitor Cells in Small Cell Lung Cancer Patients with Favorable Prognosis

“…28 -31 Multiple studies suggested that single or sequential reinfusion of PBPCs was feasible, allowing for the dose intensification of ICE by a factor of 1.80. [32][33][34][35][36][37][38][39][40][41] These studies reported significant improvements for patients with limited-disease SCLC but showed less benefit for patients with extensive-disease SCLC.…”

“…As demonstrated in our study for ICT, only the concurrent use of hematopoietic growth factors with reinfusion of autologous hematopoietic progenitor cells allowed for more significant increases in dose intensity, which translated into increased response, prolonged time to relapse, and significantly increased survival. [32][33][34][35][36][37][38][39][40] Dose intensification is an attractive option for increasing the efficacy of treatments for SCLC. Earlier studies using the ICE regimen reported promising results, but their designs provided only limited information about actual survival benefit.…”