Adjuvant Chemotherapy With Sequential or Concurrent Anthracycline and Docetaxel: Breast International Group 02-98 Randomized Trial

Background Docetaxel is more effective than doxorubicin for patients with advanced breast cancer. The Breast International Group 02-98 randomized trial tested the effect of incorporating docetaxel into anthracycline-based adjuvant chemotherapy and compared sequential vs concurrent administration of doxorubicin and docetaxel. Methods Patients with lymph node-positive breast cancer (n = 2887) were randomly assigned to one of four treatments: 1) sequential control (four cycles of doxorubicin at 75 mg/m2, followed by three cycles of cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]); 2) concurrent control (four cycles of doxorubicin at 60 mg/m2 plus cyclophosphamide at 600 mg/m2, followed by three cycles of CMF); 3) sequential docetaxel (three cycles of doxorubicin at 75 mg/m2, followed by three cycles of docetaxel at 100 mg/m2, followed by three cycles of CMF); 4) concurrent docetaxel (four cycles of doxorubicin at 50 mg/m2 plus docetaxel at 75 mg/m2, followed by three cycles of CMF). The primary comparison evaluated the efficacy of including docetaxel regardless of schedule and was planned after 1215 disease-free survival (DFS) events (ie, relapse, second primary cancer, or death from any cause). Docetaxel and control treatment groups were compared by log-rank tests, and hazard ratios (HR) of DFS events were calculated by Cox modeling. All statistical tests were two-sided. Results Due to a lower-than-anticipated rate of relapse, this analysis was performed after 5 years with 732 events. Patients in control arms had a 5-year DFS of 73% (95% confidence interval [CI] = 70% to 75%). Docetaxel treatment resulted in an improvement in DFS of borderline statistical significance compared with control treatment (HR = 0.86, 95% CI = 0.74 to 1.00; P = .05). However, DFS in the sequential docetaxel arm was better than that in the concurrent docetaxel arm (HR = 0.83, 95% CI = 0.69 to 1.00) and in the sequential control arm (HR = 0.79, 95% CI = 0.64 to 0.98). Conclusions Incorporating docetaxel into anthracycline-based therapy resulted in an improvement in DFS that was of borderline statistical significance. However, important differences may be related to doxorubicin and docetaxel scheduling, with sequential but not concurrent administration, appearing to produce better DFS than anthracycline-based chemotherap

The taxanes: toxicity and quality of life considerations in advanced ovarian cancer

The taxanes paclitaxel and docetaxel show good activity in the management of advanced ovarian cancer when used in conjunction with platinum agents. Accumulating evidence from clinical studies, particularly the latest results from the phase III comparative SCOTROC study, indicates that the two drugs confer similar rates of tumour response and survival in women with this condition. However, it is clear that paclitaxel and docetaxel differ in their tolerability profiles and in other respects, and cannot be regarded as directly equivalent drugs. In particular, paclitaxel is associated with significant neurotoxicity; peripheral neuropathy has also been reported with docetaxel, but to a lesser extent. Neutropenia appears more prevalent with docetaxel than with paclitaxel, although clinical trial data show that this adverse effect is manageable and need not compromise dose delivery. Docetaxel is also associated with potential benefits accruing from shorter infusion times and lack of need for premedication with intravenous histamine H1 and H2 antagonists. Emerging quality of life data are expected to shed further light on the overall benefit of chemotherapy in women with advanced ovarian cancer in general, and on taxane−platinum combinations in particular

Vinflunine: a new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy

To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin targeted agent vinflunine (VFL) (320 mg m−2 q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All patients had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment and subsequently received a first-line A/T combination for advanced/metastatic disease; or relapsed >6 months after completion of adjuvant A/T therapy and were subsequently treated with the alternative agent; or relapsed within 6 months from an adjuvant A/T combination. Objective response was documented in 18 of 60 patients enrolled (RR: 30% (95% confidence interval (CI): 18.9–43.2%)). Among the responders, seven patients had relapsed during a period of <3 months from taxane-based regimen yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI: 4.2–7.2), median progression-free survival was 3.7 months (95% CI: 2.8–4.2) and median overall survival was 14.3 months (95% CI: 9.2–19.6). The most frequent adverse event was neutropenia (grade 3 in 28.3% and grade 4 in 36.7% of patients). No febrile neutropenia was observed. Fatigue (grade 3 in 16.7% of patients) and constipation (grade 3 in 11.7% of patients) were also common; these were non-cumulative and manageable permitting achievement of a good relative dose intensity of 93.5%. Vinflunine is an active agent with acceptable tolerance in the management of MBC patients previously treated with (A/T)-based regimens. These encouraging phase II results warrant further investigation of this novel agent in combination with other active agents in this setting or in earlier stages of disease

Cancer of the breast: 5-year survival in a tertiary hospital in Uganda

The objective was to investigate survival of breast cancer patients at Mulago Hospital. A retrospective study of the medical records of 297 breast cancer patients referred to the combined breast clinic housed in the radiotherapy department between 1996 and 2000 was done. The female/male ratio was 24 : 1. The age range was 22–85 years, with a median of 45 years and peak age group of 30–39 years. Twenty-three percent had early disease (stages 0–IIb) and 26% had metastatic disease. Poorly differentiated was the most common pathological grade (58%) followed by moderately differentiated (33%) and well-differentiated (9%) tumours. The commonest pathological type encountered was ‘not otherwise specified' (76%). Of all patients, 75% had surgery, 76% had radiotherapy, 60% had hormonotherapy and 29% had chemotherapy. Thirty-six (12%) patients received all the four treatment modalities. The 5-year survival probabilities (Kaplan–Meier) for early disease were 74 and 39% for advanced disease (P=0.001). The overall 5-year survival was 56%, which is lower than the rates in the South African blacks (64%) and North American whites (82–88%)

5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5)

This ESO-ESMO ABC 5 Clinical Practice Guideline provides key recommendations for managing advanced breast cancer patients. It provides updates on managing patients with all breast cancer subtypes, LABC, follow-up, palliative and supportive care. Updated diagnostic and treatment algorithms are also provided. All recommendations were compiled by a multidisciplinary group of international experts. Recommendations are based on available clinical evidence and the collective expert opinion of the authors

Locally advanced breast cancer: Treatment guideline implementation with particular attention to low- and middle-income countries

The management of locally advanced breast cancer (LABC) is guided by scientific advances but is limited by local resources and expertise. LABC remains very common in low-resource countries. The Systemic Therapy Focus Group met as part of the Breast Health Global Initiative (BHGI) Summit in Budapest, Hungary, in October 2007 to discuss management and implementation of primary systemic therapy (PST) for LABC. PST is standard treatment for large operable breast cancer in enhanced-resource settings and, in all resource settings, should be standard treatment for inoperable breast cancer and for LABC. Standard PST includes anthracycline-based chemotherapy. The addition of sequential taxanes after anthracycline improves pathologic responses and breast-conservation rates and is appropriate at enhanced-resource levels; however, costs and lack of clear survival benefit do not justify their use at limited-resource levels. It remains to define better the role of endocrine therapy as PST, but it is acceptable in elderly women. Aromatase inhibitors have produced better results than tamoxifen in postmenopausal patients and are used in enhanced-resource settings. The less expensive tamoxifen remains useful in low-resource countries. Trastuzumab combined with chemotherapy yields high pathologic response rates in patients with HER2-neu-overexpressing tumors; its use in low-resource countries is limited by high costs. Most studies on PST of LABC were conducted in countries with enhanced resources. BHGI encourages conducting clinical trials in countries with limited resources. © 2008 American Cancer Society.Agarwal G, 2007, WORLD J SURG, V31, P1031, DOI 10.1007-s00268-005-0585-9; Albain KS, 2002, P AN M AM SOC CLIN, V21, p37a; Anderson BO, 2008, CANCER, V113, P2221, DOI 10.1002-cncr.23844; Anderson BO, 2006, BREAST J, V12, pS3, DOI 10.1111-j.1075-122X.2006.00199.x; ANGELL M, 2004, DRUG PRICES PHARM TR; Bear HD, 2003, J CLIN ONCOL, V21, P4165, DOI 10.1200-JCO.2003.12.005; Bear HD, 2006, J CLIN ONCOL, V24, P2019, DOI 10.1200-JCO.2005.04.1665; Bonadonna G, 1998, J CLIN ONCOL, V16, P93; Burstein HJ, 2003, J CLIN ONCOL, V21, P46, DOI 10.1200-JCO.2003.03.124; Buzdar AU, 1999, J CLIN ONCOL, V17, P3412; Buzdar AU, 2007, CLIN CANCER RES, V13, P228, DOI 10.1158-1078-0432.CCR-06-1345; Buzdar AU, 2005, J CLIN ONCOL, V23, P3676, DOI 10.1200-JCO.2005.07.032; Buzdar AU, 2007, CANCER, V110, P2394, DOI 10.1002-cncr.23083; Cataliotti L, 2007, EUR J CANCER, V43, P660, DOI 10.1016-j.ejca.2006.12.008; Cataliotti L, 2006, CANCER, V106, P2095, DOI 10.1002-cncr.21872; CLIFFORD KSC, 1999, RAD ONCOLOGY MANAGEM, P369; Davidson NE, 2005, J NATL CANCER I, V97, P159; Dawood S, 2007, CANCER, V110, P1195, DOI 10.1002-cncr.22895; Eiermann W, 2001, ANN ONCOL, V12, P1527, DOI 10.1023-A:1013128213451; El Saghir Nagi S, 2007, Int J Surg, V5, P225, DOI 10.1016-j.ijsu.2006.06.015; Ellis MJ, 2001, J CLIN ONCOL, V19, P3808; Estevez LG, 2004, CLIN CANCER RES, V10, P3249, DOI 10.1158-1078-0432.CCR-03-0133; Fisher B, 1998, J CLIN ONCOL, V16, P2672; Fregene A, 2005, CANCER-AM CANCER SOC, V103, P1540, DOI 10.1002-cncr.20978; FREUDENHEIM M, 2002, NY TIMES 1227; Goble S, 2003, SURG CLIN N AM, V83, P943, DOI 10.1016-S0039-6109(03)00071-9; Green MC, 2005, J CLIN ONCOL, V23, P5983, DOI 10.1200-JCO.2005.06.232; Greene FL, 2002, AJCC CANC STAGING MA; HALYARD MY, 2006, J CLIN ONCOL, V24; Heys Steven D, 2002, Clin Breast Cancer, V3 Suppl 2, pS69, DOI 10.3816-CBC.2002.s.015; Heys SD, 2005, BREAST CANCER RES TR, V90, P169, DOI 10.1007-s10549-004-1001-0; Hortobagyi Gabriel N, 2005, Clin Breast Cancer, V6, P391, DOI 10.3816-CBC.2005.n.043; Hurley J, 2006, J CLIN ONCOL, V24, P1831, DOI 10.1200-JCO.2005.02.8886; Hurley Judith, 2005, Clin Breast Cancer, V5, P447, DOI 10.3816-CBC.2005.n.003; Joensuu H, 2006, NEW ENGL J MED, V354, P809, DOI 10.1056-NEJMoa053028; Kaufmann M, 2003, J CLIN ONCOL, V21, P2600, DOI 10.1200-JCO.2003.01.136; Mauri D, 2005, J NATL CANCER I, V97, P188; Mauriac L, 2002, ANN ONCOL, V13, P293, DOI 10.1093-annonc-mdf037; Mauriac L, 1999, ANN ONCOL, V10, P47, DOI 10.1023-A:1008337009350; Mazouni C, 2007, ANN ONCOL, V18, P874, DOI 10.1093-annonc-mdm008; *NCCN, BREAST CANC 2008 V2; *NIH, 2007, TRAST 6 MONTHS 1 YEA; ONYANGO M, 2007, BREAST HLTH GLOB IN; Parkes A, 2006, HEALTH PLACE, V12, P1, DOI 10.1016-j.healthplace.2004.03.004; Pestalozzi BC, 2005, ANN ONCOL, V16, P7, DOI 10.1093-annonc-mdi825; Rastogi P, 2008, J CLIN ONCOL, V26, P778, DOI 10.1200-JCO.2007.15.0235; Rodriguez-Cuevas S, 2001, CANCER, V91, P863, DOI 10.1002-1097-0142(20010215)91:4863::AID-CNCR10743.0.CO;2-Y; Sachelarie I, 2006, ONCOLOGIST, V11, P574, DOI 10.1634-theoncologist.11-6-574; Semiglazov VF, 2007, CANCER-AM CANCER SOC, V110, P244, DOI 10.1002-cncr.22789; Shyyan R, 2008, CANCER-AM CANCER SOC, V113, P2257, DOI 10.1002-cncr.23840; SILVA OE, 2005, BREAST CANC PRACTICA, P251; SINGLETARY SE, 2002, J CLIN ONCOL, V20, P3629; Smigal C, 2006, CA-CANCER J CLIN, V56, P168; Smith IC, 2002, J CLIN ONCOL, V20, P1456, DOI 10.1200-JCO.20.6.1456; Smith IE, 2005, J CLIN ONCOL, V23, P5108, DOI 10.1200-JCO.2005.04.005; Thomas E, 2004, J CLIN ONCOL, V22, P2294, DOI 10.1200-JCO.2004.05.207; *US FDA, DRUG PAT; von Minckwitz G, 2007, EXPERT OPIN PHARMACO, V8, P485, DOI 10.1517-14656566.8.4.485; WAGSTAFF A, 2006, CANC WORLD; Wolmark N, 2001, J NATL CANC I MONOGR, V30, P96; World Health Organization, 2005, ESS MED WHO MOD LIST; ZIELINSKI S, 2005, J NATL CANCER I, V97, P15726252