Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial

Neutropenia following high-dose chemotherapy leads to a high incidence of infectious complications, of which central venous catheter-related infections predominate. Catheter-related infections and associated risk factors in 392 patients participating in a randomized adjuvant breast cancer trial and assigned to receive high-dose chemotherapy and peripheral stem-cell reinfusion were evaluated. Median catheter dwell time was 25 days (range 1-141). Catheter-related infections were seen in 28.3% of patients (11 infections per 1000 catheter-days). Coagulase-negative staphylococci were found in 104 of 186 positive blood cultures (56%). No systemic fungal infections occurred. Cox regression analysis showed that duration of neutropenia 410 days (P ¼ 0.04), using the catheter for both stem-cell apheresis and high-dose chemotherapy (P ¼ o0.01), and use of total parenteral nutrition (TPN, P ¼ 0.04) were predictive for catheter-related infections. In conclusion, a high incidence of catheter-related infections after high-dose chemotherapy was seen related to duration of neutropenia, use of the catheter for both stem-cell apheresis and high-dose chemotherapy, and use of TPN. Selective use and choice of catheters could lead to a substantial reduction of catheter-related infectious complications.

Section: Introductionmentioning

confidence: 97%

Factors influencing catheter-related infections in the Dutch multicenter study on high-dose chemotherapy followed by peripheral SCT in high-risk breast cancer patients

Nieboer

Vries

Mulder

et al. 2008

“…New information provided from phase III trials [23][24][25] suggests that HDC may still have a role in subgroups of patients with BC, both in the adjuvant setting and for metastatic disease mainly when risk factors and biological parameters are considered.…”

Section: Introductionmentioning

confidence: 99%

Long-term survival in patients with metastatic breast cancer receiving intensified chemotherapy and stem cell rescue: data from the Italian registry

Martino¹,

Ballestrero

Zambelli

et al. 2012

on behalf of Gruppo Italiano per il Trapianto di Midollo Osseo, Cellule staminali emopoietiche e terapia cellulare (GITMO) -Sezione Tumori SolidiThe median survival of women with metastatic breast cancer (MBC) is 18-24 months, and fewer than 5% are alive and disease free at 5 years. We report toxicity and survival in a cohort of MBC patients receiving high-dose chemotherapy (HDC) with autologous hematopoietic SCT (AHSCT) in Italy between 1990 and 2005. Data set for survival analysis has been obtained for 415 patients. Clinical parameters including probability of transplant-related mortality (TRM), PFS and OS. With a median follow-up of 27 months (range 0-172), OS and PFS at 5 and 10 years in the whole population were 47/23 and 32/14%, respectively. A total 239 patients are alive with a median follow-up of 33 months (range 2-174). Survival was significantly more pronounced in patients harboring hormone receptor positive tumors (P ¼ 0.028), without visceral metastases (P ¼ 0.009) and in women with chemosensitive disease (Po0.0001). Sixty eight patients (20.4%) who received HDC in partial response, stable or progressive disease underwent conversion to CR. TRM was 2.5% overall and 1.3% since 2000. Our findings suggest that could be a role for HDC and AHSCT in delaying disease progression and possibly cure a subset of MBC patient harboring chemosensitive tumors.

“…While the first-and early secondgeneration randomized transplant trials in the adjuvant settings suggest a benefit in disease-free survival (DFS) in some of the trials, there appears to be no survival benefit in any of the randomized trials except for one. [1][2][3][4][5][6][7] It has been hypothesized that when patients relapse, it is from presumed sub-clinical occult disease and this can be in either the adjuvant or metastatic setting. Many approaches have been employed to tackle the issue of sub-clinical occult disease that includes consolidation at sites of bulk disease (by surgery or radiation), hormonal manipulation and various immunotherapeutic manipulations.…”

Section: Introductionmentioning

confidence: 99%

Randomized trial of low-dose interleukin-2 vs cyclosporine A and interferon-γ after high-dose chemotherapy with peripheral blood progenitor support in women with high-risk primary breast cancer

Vahdat

Cohen

Zipin

et al. 2007

High-risk primary breast cancer patients treated with high-dose chemotherapy (HDC) and stem cell support (SCS) have shown prolonged disease-free survival (DFS) in many studies; however, only one trial has demonstrated an overall survival benefit (OS). We hypothesize that the period following myeloablative therapy is ideal for immunologic manipulation and studied the effects of two different methods of immunotherapy following HDC with SCS aimed at the window of immune reconstitution. Seventy-two women with high-risk stage II or III breast cancer were randomized following HDC to receive either interleukin 2 (IL-2) at 1 million units/m 2 SQ daily for 28 days or combined cyclosporine A (CsA) at 1.25 mg/kg intravenously daily from day 0 to þ 28 and interferon gamma (IFN-c) 0.025 mg/m 2 SQ every 2 days from day þ 7 to þ 28. At a median follow-up of 67 months, no significant difference was observed in DFS or OS between the two treatment groups. The IL-2 arm had a 59% DFS (95% CI (0.45, 0.78)) and a 72% OS (95% CI (0.58, 0.88)) at 5 years. The CsA/INF-c arm had a similar outcome with a 55% DFS (95% CI (0.40, 0.76)) and a 78% OS (95% CI (0.65, 0.94)) at 5 years. Treatment was well tolerated, without increased toxicity.