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.
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 < or = 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.
Oelmann
E
E
Department of Medicine/Hematology, University Hospitals, Münster, Germany.
Thomas
M
M
Serve
H
H
Kienast
J
J
Zühlsdorf
M
M
Mohr
M
M
Klinke
F
F
Dölken
G
G
Macha
H
H
Schmidt
E W
EW
Berdel
W E
WE
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000628:therapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006402:Hematologic Diseases / Q000139:chemically induced; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide