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.
Weill Cornell Medical College, New York, NY 10021, USA.
L T
LT
Vahdat
C
C
Balmaceda
K
K
Papadopoulos
D
D
Frederick
D
D
Donovan
E
E
Sharpe
E
E
Kaufman
D
D
Savage
A
A
Tiersten
G
G
Nichols
J
J
Haythe
A
A
Troxel
K
K
Antman
C S
CS
Hesdorffer
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