High-dose Chemotherapy For Metastatic Breast Cancer Research Articles

Long-term survival after high-dose chemotherapy with autologous hematopoietic cell transplantation in metastatic breast cancer

The most common indication for high-dose chemotherapy (HDC) and autologous hematopoietic cell transplantation (AHCT) in the 1990s was breast cancer. Several randomized trials and a more recent meta-analysis failed to show a survival benefit for AHCT in metastatic breast cancer (MBC); however, they demonstrated a better-than-expected 10-year to 15-year survival in 5-15% of patients. We thus evaluated the long-term results of treatment with HDC and AHCT in MBC at our institution. From 1984 to 2000, 285 patients underwent AHCT for MBC. The patient characteristics were collected through the Cleveland Clinic, United Transplant Database. A retrospective review of the medical records of the long-term surviving breast-cancer patients treated with HDC and AHCT was conducted. With a median follow-up of 169 months, 34 (12%) remain alive. Of the 251 patients who died, 218 (87%) died of metastatic disease. A comparison by age (<50 years and >50 years) and hormonal status did not demonstrate any differences in relapse (p=.33 and p=.32, respectively) or survival (p=.13 and p=.42). Of the 34 long-term survivors, sufficient data were available on 28 patients, and further evaluation revealed that the majority had a primary or locally recurrent oligometastatic disease. This retrospective evaluation of patients who underwent AHCT for MBC demonstrates long-term survival in a small subset of patients, primarily those with primary or recurrent oligometastatic disease. Oligometastatic breast cancer is a distinct entity within MBC, which may be curable with multimodality therapy. We thus conclude there remains no overall-survival benefit to HDC in MBC.

Characteristics associated withlong-term progression-free survival following high-dose chemotherapyin metastatic breast cancer and influence of chemotherapy dose

BackgroundThe purpose of this study was to characterize long-term progression-freesurvivors (LTPFS) of metastatic breast cancer (MBC) following high-dosechemotherapy (HDCT) with autologous stem cell transplantation (ASCT)and to assess the influence of chemotherapy dose in order to identifypatients who derive major benefit from this approach. Patients and methodsWe compared patient and tumor characteristics of 16 LTPFS withthe characteristics of 118 MBC patients who received HDCT with ASCTat our institution between 1992 and 2000. To estimate the cumulativedose of chemotherapy received, the summation dose intensity product(SDIP) of the different chemotherapy regimens was calculated asrecently described by Hryniuk et al. The SDIP of the induction regimenswas added to that of the HDCT regimens to yield the total SDIP ofthe chemotherapy received. Multivariate analysis was performed todescribe the influence of the total SDIP and other prognostic factorson progression-free survival (PFS). ResultsLTPFS were mostly ≤50 years of ageand had limited, chemotherapy-sensitive, hormone-responsive MBC.Due to an apparent dose–survival relationship, an increaseby 10 units (U) in the SDIP increased the PFS time by 3 months.Independent predictors of an improved PFS were positive estrogen receptors(P = 0.001), positive combined hormonereceptors (P = 0.020), and a completeremission/no evidence of disease status after HDCT (P <0.001).In patients who had a disease-free interval (DFI) >24months after primary surgery, an SDIP of >55 U was independentlyassociated with a longer PFS [hazard ratio (HR) = 2.73;95% confidence interval 1.29–5.81; P = 0.009]. ConclusionHDCT can achieve long-term PFS in young MBC patients with limited,hormone-responsive and chemotherapy-sensitive disease. After a DFI >24months, a longer PFS is associated with a higher chemotherapy doseas measured by SDIP. These retrospective analyses suggest SDIP mightbe a tool for studying cumulative dose as a determinant of outcomeof MBC chemotherapy. Thus far, however, we cannot clearly identifyany subgroup of MBC patients in whom HDCT with ASCT is of particularbenefit.

High-dose chemotherapy with haematopoietic rescue: application to primary management of metastatic breast cancer.

The development of more effective treatment strategies currently provides the only realistic hope of reducing breast cancer mortality. Among such treatments, the use of high-dose chemotherapy (HDC) has been proposed as a potentially curative strategy. Consideration of the factors involved in the successful treatment of human tumours suggests that HDC is rationally planned with regard to tumour kinetics as well as chemotherapy sensitivity and resistance patterns. Ideally HDC should include dose escalation of at least 5-10-fold of drugs shown to have a steep dose-response curve and that have been effective in first-line treatment of breast cancer. Many current chemotherapy regimens lack one or the other of these attributes. Two randomized studies of HDC in breast cancer have been recently published. In the first study, HDC using a combination of cyclophosphamide, mitoxantrone and VP-16 as initial treatment was compared with a conventional-dose regimen consisting of cyclophosphamide, mitoxantrone and vincristine. The second study compared the effects of early or delayed HDC in patients who had achieved an optimal response to conventional-dose 'induction' chemotherapy. Both studies showed HDC to be more effective than conventional-dose treatment in delaying time to progression but only the study that used HDC as initial treatment showed an effect of HDC on survival. The differences between these two investigations can probably be explained on the basis of the different effects on tumour kinetics and the efficiency of HDC when used as salvage therapy in the delayed HDC group. The finding that 20-25% of patients receiving HDC for metastatic breast cancer show prolonged disease-free survival suggest that HDC has an established role in the treatment of breast cancer. Attention now needs to turn to methods of optimizing this treatment strategy.