A phase I dose escalation study of multicyclic, dose-intensive chemotherapy with peripheral blood stem cell support for small cell lung cancer

Abstract

1,2 Models of the development of cytotoxic drug resistance suggest that maximal initial treatment will reduce the risk of relapse.3,4 Although small cell lung cancer (SCLC) is the histologic type most sensitive to combination chemotherapy, the majority of SCLC patients relapse with chemoresistant tumors. Circumvention of this secondary chemoresistance has been addressed using different treatment modalities.In a recent study, patients with limited-disease SCLC were randomly assigned to receive higher-or lower-dose cyclophosphamide and cisplatin during the first course of a cisplatin, etoposide, doxorubicin and cyclophosphamide regimen followed by five additional cycles at standard doses.5 A moderate increase in the cisplatin and cyclophosphamide doses during the first course resulted in a 17% increase in 2-year survival. However, myelosuppression is the limiting toxicity for this chemotherapy regimen.For the majority of drugs, myelosuppression is the initial dose-limiting toxicity. While hematopoietic growth factors have been utilized to reduce the toxicity and improve delivery of the planned dose, only a modest increase in dose intensity can be achieved.Recently, peripheral blood stem cells (PBSCs) have been used as a source of stem cells and shown to restore hematopoietic functions rapidly after PBSC autografting. Highdose chemotherapy with PBSC rescue has been used for leukemia and lymphoma, but for most chemosensitive solid tumors, a single high-dose chemotherapy as late intensification does not appear to prolong survival. 6 Since adjustments of the dose of cytotoxic drugs, as well as shortening of the intervals between courses, can increase dose intensity, multicyclic chemotherapy may offer the opportunity to maximize dose intensity of the treatment.

Limited-Stage Small-Cell Lung Cancer: The Current Status of Combined-Modality Therapy

“…The most common agents explored have been paclitaxel, irinotecan, topotecan, and ifosfamide. [66][67][68][69][70][71] As shown in Table 3, although response rates are high in many of the trials, the median survival times and 2-year survival rates are not impressive when compared with the phase III results seen in INT 0096 (median survival time and 2-year survival rate of 23 months and 44%, respectively).…”

A novel intensive induction therapy for high‐risk neuroblastoma utilizing sequential peripheral blood stem cell collection and infusion as hematopoietic support

“…One strategy to decrease myelosuppression and maintain dose intensity is to infuse autologous peripheral blood stem cell (PBSC) after chemotherapy as hematopoietic support. Clinical trials using PBSC between submyeloablative chemotherapy courses have successfully increased dose intensity by delivering chemotherapy at shorter intervals in patients with breast cancer, lung cancer, adult sarcomas, germ cell tumors, pediatric brain tumors, and pediatric soft tissue sarcomas 25–33.…”

Successful liquid storage of peripheral blood stem cells at subzero non-freezing temperature

“…3 The treatment regimen is shown in Table 1. Briefly, patients were treated with multiple cycles of ICE (ifosfamide 7 g/m 2 i.v.…”

“…2,3 Moreover, we and others have demonstrated that sequential reinfusion of peripheral blood stem cells (PBSC) can increase the dose intensity of the chemotherapy. 3,4 For successful transplantation, PBSC must be stored in a way that preserves their viability. Despite the enormous progress that has been made, there are still major problems with regard to this cryopreservation.…”