Phase II trial of sequential high-dose chemotherapy with paclitaxel, melphalan and cyclophosphamide, thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer.
A single high-dose cycle of chemotherapy can produce response rates in excess of 50%. However, disease-free survival (DFS) is 15-20% at 5 years. The single most important predictor of prolonged DFS is achieving a complete response (CR). Increasing the proportion of patients who achieve a complete response may improve disease-free survival. Women with metastatic breast cancer and at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and G-CSF. The first intensification was paclitaxel (825 mg/m(2)), the second melphalan (180 mg/m(2)) and the third consisted of cyclophosphamide 6000 mg/m(2) (1500 mg/m(2)/day x 4), thiotepa 500 mg/m(2) (125 mg/m(2)/day x 4) and carboplatin 800 mg/m(2) (200 mg/m(2)/day x 4) (CTCb). Sixty-one women were enrolled and 60 completed all three cycles. Following the paclitaxel infusion most patients developed a reversible, predominantly sensory polyneuropathy. Of the 30 patients with measurable disease, 12 converted to CR, nine converted to a PR*, and five had a further PR, giving an overall response rate of 87%. The toxic death rate was 5%. No patient progressed on study. Thirty percent are progression-free with a median follow-up of 31 months (range 1-43 months) and overall survival is 61%. Three sequential high-dose cycles of chemotherapy are feasible and resulted in a high response rate. The challenge continues to be maintenance of response and provides the opportunity to evaluate strategies for eliminating minimal residual disease.
Vahdat
L T
LT
Weill Cornell Medical College, New York, NY 10021, USA.
Balmaceda
C
C
Papadopoulos
K
K
Frederick
D
D
Donovan
D
D
Sharpe
E
E
Kaufman
E
E
Savage
D
D
Tiersten
A
A
Nichols
G
G
Haythe
J
J
Troxel
A
A
Antman
K
K
Hesdorffer
C S
CS
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D001943:Breast Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage / Q000633:toxicity; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage / Q000633:toxicity; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000633:toxicity; D036102:Peripheral Blood Stem Cell Transplantation; D011115:Polyneuropathies / Q000139:chemically induced; D012074:Remission Induction; D016019:Survival Analysis; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage / Q000633:toxicity
D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin; D017239:Paclitaxel; D008558:Melphalan