Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement

• Published in: The Lancet (British edition) Vol. 352; no. 9127; pp. 515 - 521
• Main Authors: Rodenhuis, Sjoerd, Richel, Dick J, van der Wall, Elsken, Schornagel, Jan H, Baars, Joke W, Koning, Caro CE, Peterse, Johannes L, Borger, Jacques H, Nooijen, Willem J, Bakx, Roel, Dalesio, Otilia, Rutgers, Emiel
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 15.08.1998; Lancet; Elsevier Limited
• Subjects: Antibiotics, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - administration & dosage; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Axilla; Biological and medical sciences; Breast cancer; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Carboplatin - administration & dosage; Chemotherapy; Chemotherapy, Adjuvant; Clinical trials; Cyclophosphamide - administration & dosage; Disease-Free Survival; Drug Administration Schedule; Epirubicin - administration & dosage; Estrogen Antagonists - administration & dosage; Female; Fluorouracil - administration & dosage; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Lymphatic Metastasis - pathology; Medical sciences; Middle Aged; Neoplasm Staging; Pharmacology. Drug treatments; Radiotherapy, Adjuvant; Survival Rate; Tamoxifen - administration & dosage; Thiotepa - administration & dosage; Antineoplastic agent; Human; Carcinoma; Adjuvant treatment; Malignant tumor; Metastasis; Precursor; Periphery; Mammary gland diseases; Chemotherapy; Blood cell; Randomization; Axillary ganglion; Phase II trial; Feasibility; Mammary gland; High dose
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(98)01350-6

Uncontrolled studies suggest that high-dose chemotherapy is beneficial in patients with breast cancer and multiple metastases to the axillary lymph nodes. Many physicians accept this treatment as standard care. We aimed to assess adjuvant high-dose chemotherapy in breast cancer in a phase II randomised trial. 97 women aged younger than 60 years, who had breast cancer with extensive axillary-node metastases (confirmed by a tumour-positive infraclavicular lymph-node biopsy), received three courses of up-front chemotherapy (FE 120C). This regimen consisted of cyclophosphamide 500 mg/m 2, epirubicin 120 mg/m 2, and 5-fluorouracil 500 mg/m 2 once weekly for 3 weeks. After surgery, stable patients or those who responded to chemotherapy were randomly assigned conventional therapy (fourth course of FE 120C, followed by radiation therapy and 2 years of tamoxifen [40 patients]) or high-dose therapy (identical treatment but an additional high-dose regimen and peripheral-blood progenitor-cell [PBPC] support after the fourth FE 120C course [41 patients]). This high-dose regimen comprised cyclophosphamide 6 g/m 2, thiotepa 480 mg/m 2, and carboplatin 1600 mg/m 2. The primary endpoint was overall and disease-free survival. All analyses were by intention to treat. No patients died from toxic effects of chemotherapy. With a median follow-up of 49 (range 21–76) months, the 4-year overall and relapse-free survivals for all 97 patients were 75% and 54%, respectively. There was no significant difference in survival between the patients on conventional therapy and those on high-dose therapy. High-dose therapy is associated with substantial cost and acute toxic effects, but also has potentially irreversible long-term effects. Until the benefit of this therapy is substantiated by large-scale phase III trials, high-dose chemotherapy should not be used in the adjuvant treatment of breast cancer, apart from in randomised studies.