Double dose-intensive chemotherapy with autologous marrow and peripheral-blood progenitor-cell support for metastatic breast cancer: a feasibility study

• Published in: Journal of clinical oncology Vol. 12; no. 1; p. 37
• Main Authors: Ayash, L J, Elias, A, Wheeler, C, Reich, E, Schwartz, G, Mazanet, R, Tepler, I, Warren, D, Lynch, C, Gonin, R
• Format: Journal Article
• Language: English
• Published: United States 01.01.1994
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bone Marrow Diseases - chemically induced; Bone Marrow Diseases - prevention & control; Bone Marrow Transplantation; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Carboplatin - administration & dosage; Carboplatin - adverse effects; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Feasibility Studies; Female; Granulocyte Colony-Stimulating Factor - therapeutic use; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Neoplasm Metastasis; Remission Induction; Survival Analysis; Thiotepa - administration & dosage; Thiotepa - adverse effects; Treatment Outcome
• ISSN: 0732-183X
• DOI: 10.1200/JCO.1994.12.1.37

Twenty-seven percent of responding metastatic breast cancer patients remain progression-free a median 29 months following one intensification course of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). European investigators report high complete response (CR) rates with melphalan for breast cancer. This trial studied the feasibility of two tandem high-dose intensification therapies in an attempt to optimize disease response and duration. Women with at least partial responses (PRs) to induction therapy received melphalan (140 to 180 mg/m2), followed 24 hours later by chemotherapy and granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral-blood progenitor cells (PBPCs) and subsequent G-CSF until WBC recovery. The women were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. Twenty women were assessable. Fourteen (70%) required admission for fever (10% infection) or mucositis (35%) after melphalan (median stay, 5 days). Median days of absolute neutrophil count (ANC) less than 500/microL and platelet count less than 20,000/microL were 6 and 5.5, respectively. Patients received CTCb 25 days after starting melphalan and had a hospital stay of 25 days. After CTCb, median days of ANC less than 500/microL and platelet count less than 20,000/microL were 11.5 and 24, respectively. Grade 3 toxicities included venoocclusive disease (VOD) (10%), mucositis (45%), and infection (20%). Toxicities were reversible without mortality. With mobilized PBPCs and growth factors, double dose-intensive chemotherapy is feasible with acceptable toxicity. When compared with trials using marrow alone, these supportive adjuncts decrease sepsis and organ toxicity. The concepts of dose and dose-intensity may now be more effectively and safely studied in chemosensitive tumors, including breast cancer.