The emergence of
chemotherapy has dramatically improved both quality of life and survival in patients with
small cell lung cancer (SCLC). Nonetheless, achieving long-term survival in SCLC patients has been a problem. Early studies of
combination chemotherapy with
cyclophosphamide/
doxorubicin/
vincristine (CAV) and
cyclophosphamide/
methotrexate/
lomustine/
vincristine (CMCV) reported impressive response rates in patients with SCLC.
Ifosfamide, an analogue of
cyclophosphamide, has demonstrated single-agent activity against SCLC, achieving overall response rates ranging from 5.6% to 76.5%. Because of this, and because of the agent's proven synergism in
combination chemotherapy for recurrent
testicular cancer and its relative non-myelosuppressive qualities (compared with
cyclophosphamide), the incorporation of
ifosfamide into
combination chemotherapy for SCLC was rational. The Hoosier Oncology Group reported high response rates with VIP (
ifosfamide combined with
etoposide/
cisplatin) in SCLC patients and proved the superiority of VIP over
etoposide/
cisplatin in patients with extensive disease. Presently, this group is evaluating the role of chronic oral
etoposide as
maintenance chemotherapy for patients with extensive SCLC that responds to initial VIP treatment.
Salvage treatment with daily oral
etoposide has also produced encouraging results, leading the Hoosier Oncology Group to incorporate oral
etoposide as part of the
VIP regimen (VoIP). It is currently unclear whether
combination chemotherapy containing daily oral
etoposide will have a major impact on survival. Further trials of
combination chemotherapy with newer active agents like
paclitaxel and
topotecan, as well as with proven single agents like
ifosfamide, are clearly warranted to improve the outcome of patients with SCLC.