A short course of induction chemotherapy followed by two cycles of high-dose chemotherapy with stem cell rescue for chemotherapy naive metastatic breast cancer: sequential phase I/II studies.
Two cycles of high-dose chemotherapy with stem cell support (HDC) may increase the total dose delivered and dose intensity. A brief induction phase and different non-cross-resistant agents for each HDC cycle were used to avoid drug resistance. Twenty-six women with metastatic BC had induction and stem cell mobilization with two cycles of doxorubicin/G-CSF given every 14 days. Patients with stable disease or better after induction received HD CTCb followed by HD melphalan and dose-escalated paclitaxel. At 475 mg/m(2) of paclitaxel by 24-h infusion, dose-limiting transient peripheral sensory neuropathy was encountered. No toxic deaths occurred. Complete and near complete response after completion of therapy was achieved in 22 (85%) of 26 patients. The median EFS was 38 months. The median OS has not yet been reached. At a median follow-up of 33 (25-43) months, actuarial EFS and OS were 54% (95% confidence interval (CI), 39-69%) and 69% (95% CI, 56-79%), respectively. This double transplant approach lasts only 14 weeks and is feasible, safe, and tolerable. Whilst selection biases may in part contribute to favorable EFS and OS, a randomized comparison of standard therapy vs double transplant in both metastatic and locally advanced breast cancer is warranted.
Elias
A D
AD
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Richardson
P
P
Avigan
D
D
Ibrahim
J
J
Joyce
R
R
McDermott
D
D
Levine
J
J
Warren
D
D
McCauley
M
M
Wheeler
C
C
Frei
E
E
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction / Q000379:methods; D015996:Survival Rate; D017211:Treatment Failure; D016896:Treatment Outcome
D004317:Doxorubicin; D017239:Paclitaxel; D008558:Melphalan