Use of doxorubicin plus cyclophosphamide followed by docetaxel as adjuvant chemotherapy for breast cancer

We evaluated the feasibility and incidence of hematological toxicity in a series of 39 breast cancer patients treated at our institute with doxorubicin plus cyclophosphamide (AC) followed by docetaxel, using prophylactic G-CSF (pegfilgrastim). We prescribed G-CSF as secondary prophylaxis during the AC regimen and as primary prophylaxis during treatment with docetaxel. For the AC treatment, we recorded 6 cases of grade III (15.3%) and one case of grade IV (2.5%) neutropenia; we found one case of Grade IV anemia. For the docetaxel regimen, we registered one case of Grade IV (2.5%) neutropenia and three cases of Grade III leukopoenia without neutropenia. No patients experienced cardiac symptoms or baseline LVEF rate decrease. All patients concluded the programmed chemotherapy. Our experience shows the safety of docetaxel in combination with anthracyclines and the efficacy of prophylaxis with G-CSF in breast cancer adjuvant chemotherapy.     

The cost-utility of adjuvant chemotherapy using docetaxel and cyclophosphamide compared with doxorubicin and cyclophosphamide in breast cancer

Purpose

The adoption of a chemotherapeutic regimen in oncologic practice is a function of both its clinical and its economic impacts on cancer management. For breast cancer, U.S. Oncology trial 9735 reported significant improvements in disease-free and overall survival favoring adjuvant tc (docetaxel 75 mg/m² and cyclophosphamide 600 mg/m² every 3 weeks for 4 cycles) compared with ac (doxorubicin 60 mg/ m² and cyclophosphamide 600 mg/m² every 3 weeks for 4 cycles). We carried out an economic evaluation to examine the cost–utility of adjuvant tc relative to ac, in terms of cost per quality-adjusted life year (qaly) gained, given the improved breast cancer outcomes and higher costs associated with the tc regimen.

Methods

A Markov model was developed to calculate the cumulative costs and qalys gained over a 10-year horizon for hypothetical cohorts of women with breast cancer treated with ac or with tc. Event rates, costs, and utilities were derived from the literature and local resources. Efficacy and adverse events were based on results reported from U.S. Oncology trial 9735. The model takes a third-party direct payer perspective and reports its results in 2008 Canadian dollars. Costs and benefits were both discounted at 3%.

Results

At a 10-year horizon, tc was associated with $3,960 incremental costs and a 0.24 qaly gain compared with ac, for a favorable cost–utility of $16,753 per qaly gained. Results were robust to model assumptions and input parameters.

Conclusions

Relative to ac, tc is a cost-effective adjuvant chemotherapy regimen, with a cost-effectiveness ratio well below commonly applied thresholds.     

HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer.

PURPOSE: Human epidermal growth factor receptor 2 (HER2) overexpression was found to predict a good response in breast carcinoma patients treated with doxorubicin (Adriamycin [ADM]). Evidence from our recent study indicates that node-positive patients respond to cyclophosphamide, methotrexate, and fluorouracil (CMF) regardless of HER2 status. We address the issue of whether therapy regimens including CMF and ADM versus CMF alone have the same therapeutic effect in patients with HER2+ and HER2- tumors in terms of relapse-free survival (RFS) and overall survival (OS). METHODS: Archival specimens of the primary tumors from 506 patients in a prospective clinical trial were stained with the anti-HER2 monoclonal antibody CB11. Originally, patients were randomly allocated to receive either 12 courses of intravenous CMF or eight courses of the same regimen followed by four cycles of ADM. RFS and OS were analyzed by a Cox model taking into account treatment, HER2 status, and the interaction between treatment and HER2 status, adjusting for the effect of other known clinical and biopathologic factors. RESULTS: Analysis of survival rates indicates a possible differential effect of treatment in the patients grouped according to HER2 status. Improved RFS and OS were observed in the HER2+ subgroup after treatment with CMF plus ADM versus CMF alone. With a median follow-up of 15 years, the hazard ratio (HR) for RFS was 0.83 in HER2+ tumors and 1.22 in HER2- tumors. The effect of treatment was more evident on OS in HER2+ patients (HR = 0.61; CI, 0.32 to 1.16) than in HER2- patients (HR = 1.26). CONCLUSION: Our data indicate that adding ADM to CMF might be beneficial for patients with HER2+ tumors.     

Cost-effectiveness analysis of adjuvant therapy for node positive breast cancer in Korea: docetaxel, doxorubicin and cyclophosphamide (TAC) versus fluorouracil, doxorubicin and cyclophosphamide (FAC)

Background This study evaluated the incremental cost–effectiveness (ICER) and cost–utility ratios (ICUR) of TAC compared with FAC following primary surgery for node positive breast cancer patients in Korea. Materials and methods A cost–effectiveness analysis was performed using the Markov model from the combined view of Korean National Health Insurance and patients. The model allowed assessment from the beginning of the first cycle of adjuvant chemotherapy following primary surgery until death. Relevant clinical data were obtained from the clinical trial BCIRG 001 and data for local treatment patterns and direct medical costs were obtained from three Korean hospitals. Results Over a life time horizon, the life expectancy of TAC was 0.9 years longer than that of FAC. The ICER was 8,025,879 Korean won (KW, €6,573) per life year gained and the ICUR was 8,885,794 KW (€7,277) per QALY gained when the cost and effectiveness were discounted at 5%. The model was most sensitive to the percent patient receiving prophylactic granulocyte colony stimulating factor (G-CSF) in TAC arm and the ICUR was 12,119,561 KW (€9,926) when assuming 100%. Conclusions TAC appears to be cost–effective in the management of early breast cancer in Korea. An invited commentary to this article can be found at doi:.     

Toxicity of dose-dense docetaxel followed by doxorubicin with cyclophosphamide as adjuvant therapy for breast cancer in a phase II study

PURPOSE: In order to evaluate the feasibility of dose-dense docetaxel followed by dose-dense AC (doxorubicin/cyclophosphamide) as adjuvant chemotherapy for operable breast cancer, we conducted a phase II study. PATIENTS AND METHODS: In cohort 1, 28 patients received docetaxel 100 mg/m2 followed by doxorubicin 60 mg/m2 with cyclophosphamide 600 mg/m2, each every 2 weeks for 4 weeks (total of 8 cycles). Enrollment was discontinued because of stopping criteria based on significant toxicity (grade 4 hematologic toxicity or grade >or= 3 nonhematologic toxicity). In cohort 2, the docetaxel dose was reduced to 75 mg/m2; enrollment was discontinued after 18 patients. RESULTS: Significant toxicity occurred in 79% and 72% of patients in cohorts 1 and 2, respectively, resulting in treatment delays in 50% and 17% of patients, respectively. The most common grade 4 hematologic toxicity was neutropenia, which occurred in 7% and 42% of cohort 1 patients during docetaxel and AC, respectively, and in none and 19% of cohort 2 patients, respectively. The most common grade >or= 3 nonhematologic toxicity was palmar-plantar erythrodysesthesia, which occurred in 25% and none of cohort 1 patients during docetaxel and AC, respectively. With docetaxel 75 mg/m2 and patient education encouraging routine use of topical strategies, grade 3 palmar-plantar erythrodysesthesia occurred in only 11% of cohort 2 patients. Grade 2 nail changes were also debilitating and occurred in 33% of cohort 1 patients during AC. CONCLUSION: These phase II findings suggest that dose-dense docetaxel 100 mg/m2 followed by AC is not feasible and, until more studies are conducted, should be restricted to clinical studies.     

Evaluation of anemia, neutropenia and skin toxicities in standard or dose-dense doxorubicin/cyclophosphamide (AC)-paclitaxel or docetaxel adjuvant chemotherapy in breast cancer.

BACKGROUND: Results of CALGB 9741 demonstrated that administering standard doxorubicin/cyclophosphamide (AC)-paclitaxel therapy for adjuvant therapy of breast cancer in a dose-dense fashion with colony-stimulating factors increases efficacy, decreases severe neutropenia, but may increase the need for blood transfusions. A chart review was performed to evaluate the rates of anemia, neutropenia and skin toxicities with dose-dense and traditional AC-taxane chemotherapy. PATIENTS AND METHODS: A total of 112 patients received one of four treatments: non-dose-dense AC-paclitaxel (NDD Pac), dose-dense AC-paclitaxel (DD Pac), non dose-dense AC-docetaxel (NDD Doc), or dose-dense AC-docetaxel (DD Doc). RESULTS: Transfusion rates were not increased in the dose-dense population; however, rates of grade 2-4 anemia (23% versus 0%, P=0.029), as well as erythropoietin use (58% versus 0%, P <0.0001), were significantly increased in the DD Pac group compared with the NDD Pac group. Grade 3 skin toxicities were significantly increased in the DD Doc group compared with the NDD Doc group (70% versus 11%, P <0.0001). CONCLUSIONS: These results demonstrate that dose-dense AC-taxane therapy may increase rates of anemia and the need for erythropoietin, and decrease rates of neutropenia. The utility of DD Doc appears limited by skin toxicities and its use outside of a clinical study should not be recommended.     

Japanese experience with second-line chemotherapy with low-dose (60 mg/m2) docetaxel in patients with advanced non-small-cell lung cancer

PURPOSE: To assess the efficacy and toxicity of relatively low-dose docetaxel (60 mg/m2) for previously treated advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced (clinical stage IIIA-IV) NSCLC who had previously undergone at least one series of chemotherapy were enrolled. Previous paclitaxel use was allowed, but docetaxel was not. Docetaxel was administered at an initial dose of 60 mg/m2 intravenously on day 1 over 90 min every 3 weeks. RESULTS: From June 1997 to November 1999, 22 patients were entered into this study. The total number of cycles delivered to 22 patients was 53, with a median per patient of 2. Four patients achieved a partial response (PR), and the overall response rate was 18.2% (95% confidence interval 5.1-40.3%). The median time to progression was 13.7 weeks. The median survival time was 7.8 months, and the 1-year survival rate was 25%. About 73% of patients experienced grade 3 or 4 neutropenia. Neutropenic fever was observed in four patients (18%). Non-hematologic toxicities were generally mild. No treatment-related deaths occurred. CONCLUSIONS: Although the validity of the results of this study is limited due to the small and monoracial study population examined, low-dose (60 mg/m2) docetaxel for previously treated advanced NSCLC appears to yield antitumor activity and survival benefit comparable to those obtained with the conventional dose (100 mg/m2).     

Postoperative adjuvant chemotherapy with cisplatin,cyclophosphamide, and anthracycline (doxorubicin,epirubicin, pirarubicin) for endometrial cancer

Background Doxorubicin and cisplatin are the most commonly used chemotherapeutic agents in the treatment of endometrial cancer, but their clinical efficacy is still controversial. The aim of this study was to retrospectively assess the efficacy and toxicity of combination chemotherapy using cisplatin, cyclophosphamide, and anthracy-clines in patients with stage III/IV adenocarcinoma of the endometrium.Methods Forty patients with advanced endometrial cancer received postoperative adjuvant combination chemotherapy, using cisplatin (50 or 70mg/m²), cyclophosphamide (500mg/m²), and one of three anthracyclines (10 patients with doxorubicin [50mg/m²], 18 with epirubicin [50mg/m²], and 12 with pirarubicin [40mg/m²]), from 1987 to 1999. All patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, with pelvic lymph node dissection in 36 patients and paraaortic lymph node biopsy in 38 patients. Patients were considered eligible if they had adnexal metastasis, paraaortic lymph node metastasis, positive peritoneal cytology, or distant metastasis. The patients were divided into two groups: patients with no measurable lesion (group 1; n = 27), and those with residual measurable lesion (group 2; n = 13) after surgery. The response rate and progression-free survival rate were evaluated in group 2.Results In group 1, 7 patients (26%) had recurrence, and all of them died of the disease. No patients in stage IIIa (n = 10), however, had recurrence. In group 2, 6 of the 13 (46%) showed response to chemotherapy (complete response [CR], 31%; partial response [PR], 15%). Toxicity was moderate: 10 patients had grade 4 neutropenia; and dose reductions were mandated in 12 patients.Conclusion In group 1, the survival of patients receiving chemotherapy was considered favorable, but patients with recurrent lesions had poor prognosis. On the other hand, in group 2, the efficacy of the chemotherapy was almost equal to that reported in the literature; however, this regimen did not contribute to an improvement in the survival rate. In conclusion, a new effective regimen of postoperative adjuvant therapy is highly desirable in patients with measurable residual lesions.     

Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28.

PURPOSE: The primary aim of National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 was to determine whether four cycles of adjuvant paclitaxel (PTX) after four cycles of adjuvant doxorubicin/cyclophosphamide (AC) will prolong disease-free survival (DFS) and overall survival (OS) compared with four cycles of AC alone in patients with resected operable breast cancer and histologically positive axillary nodes. PATIENTS AND METHODS: Between August 1995 and May 1998, 3,060 patients were randomly assigned (AC, 1,529; AC followed by PTX [AC --> PTX], 1,531). Patients > or = 50 years and those younger than 50 years with estrogen receptor (ER) or progesterone receptor (PR) -positive tumors also received tamoxifen for 5 years, starting with the first dose of AC. Postlumpectomy radiotherapy was mandated. Postmastectomy or regional radiotherapy was prohibited. Median follow-up is 64.6 months. RESULTS: The addition of PTX to AC significantly reduced the hazard for DFS event by 17% (relative risk [RR], 0.83; 95% CI, 0.72 to 0.95; P = .006). Five-year DFS was 76% +/- 2% for patients randomly assigned to AC --> PTX compared with 72% +/- 2% for those randomly assigned to AC. Improvement in OS was small and not statistically significant (RR, 0.93; 95% CI, 0.78 to 1.12; P = .46). Five-year OS was 85% +/- 2% for both groups. Subset analysis of the effect of paclitaxel according to hormone receptors or tamoxifen administration did not reveal statistically significant interaction (for DFS, P = .30 and P = .44, respectively). Toxicity with the AC --> PTX regimen was acceptable for the adjuvant setting. CONCLUSION: The addition of PTX to AC resulted in significant improvement in DFS but no significant improvement in OS with acceptable toxicity. No significant interaction between treatment effect and receptor status or tamoxifen administration was observed.     

Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer

PURPOSE: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). METHODS AND MATERIALS: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weeklyx12 weeks (60 mg/m2), or every 3 weeksx4 cycles (135-175 mg/m2). Radiation fields and schedules were determined by the patient's surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. RESULTS: Weekly paclitaxel treatment at 60 mg/m2 per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135-175 mg/m2. However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. CONCLUSIONS: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury.     

Verbal memory in breast cancer patients treated with chemotherapy with doxorubicin and cyclophosphamide

Memory is one of the crucial human cognitive functions, and deficits in memory processes may lead to difficulties in everyday functioning. The aim of this study was to analyse the effect of anthracycline‐based adjuvant chemotherapy (AC) used in breast cancer treatment on verbal memory and learning. We also evaluated the relationship between verbal memory and psychological, somatic and socio‐demographic factors. The study was carried out on a group of 31 women with early breast cancer treated with adjuvant chemotherapy and 30 healthy controls. The patients underwent neuropsychological assessment using the Rey Auditory Verbal Learning Test at three time points: before chemotherapy, mid‐chemotherapy and post‐chemotherapy. The examination in the controls was conducted at the same time intervals. We found an association between AC‐schema chemotherapy and deficits in delayed memory. A deterioration in performance after treatment was observed in 19% of patients. The results showed no deterioration of immediate memory or the verbal learning process. Moreover, a positive relationship was shown between the level of education, physical fitness and the functioning of verbal memory. The results of the study also indicate that age and hormonal status are factors that may increase the possibility of deficits in verbal memory after AC‐schema chemotherapy.     

Neoadjuvant and adjuvant chemotherapy with doxorubicin and docetaxel in locally advanced breast cancer

Fifty patients with histologically confirmed stage III breast cancer were enrolled in this study of doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 intravenously infused over 1 hour every 21 days with granulocyte colony-stimulating factor for 4 cycles. This was followed by surgery (mastectomy or lumpectomy) and 4 more cycles of doxorubicin/docetaxel postoperatively, then radiation and tamoxifen as indicated. Forty-six of the 50 patients (92%) completed neoadjuvant chemotherapy, and 38 patients (76%) completed adjuvant chemotherapy. Clinical response (defined as > 50% decrease in size of tumor) was achieved after 2 cycles in 37 patients (74%) and after 4 cycles in 42 of the 46 patients (91%) who finished neoadjuvant chemotherapy. Pathologic complete response (pCR; no pathologic invasive cancer) at the primary site was obtained in 7 of 46 patients (15%); 11 had no residual gross disease but did have microscopic persistence or microscopic complete response (mCR), for a combined pCR and mCR of 18 of 46 patients (39%). No treatment-related deaths occurred, but 3 patients died during treatment: 1 from progressive disease, 1 from a gastrointestinal bleeding, and 1 from unexplained sudden cardiac death. Dose-limiting toxicities were hematologic (grade 3 neutropenia in 5 patients and grade 4 in 23 patients). Congestive heart failure developed in 4 of 50 patients (8%), with a mean decrease in left ventricular ejection fraction (LVEF) of 20% in affected patients and 1 asymptomatic decrease in LVEF of 25%. At last follow-up, 10 patients had died of progressive disease, and 1 each from sudden cardiac death and lower gastrointestinal bleeding. In locally advanced breast cancer, neoadjuvant doxorubicin/docetaxel is a very active regimen that achieved pCR of 15% and a combined pCR and mCR of 39%, for an overall clinical response rate of 91%. Adjuvant chemotherapy was complicated by dropouts and congestive heart failure. This regimen should be used with close monitoring of cardiac function.     

Clinical comparison on the safety and efficacy of fluorouracil/pirarubicin/cyclophosphamide (FPC) with fluorouracil/ epirubicin/cyclophosphamide (FEC) as postoperative adjuvant chemotherapy in breast cancer

Objective: To compare the safety and efficacy of a combination of 5-Fu, pirarubicin and CTX (FPC) withFEC as a postoperative adjuvant chemotherapy for breast cancer. Methods: A total of 655 breast cancer patientswere treated postoperatively in Jiangsu Cancer Hospital and Research Institute from 1995-2005, 292 were treatedwith FPC (5-Fu 500mg/m2 iv gtt on day 1, pirarubicin 40mg/m2 iv on day 1, CTX 500mg/m2 iv on day 1 and acycle repeated every 21-28 days for totally 4-6 cycles); 363 with FEC (5-Fu 500mg/m2 iv gtt on day 1, epirubicin50mg/m2 iv on day 1 and day 2, CTX 500mg/m2 iv on day 1 and a cycle repeated every 21-28 days for totally4-6 cycles). Toxicity was evaluated after each cycle of chemotherapy. Results: Main side effects in both FPC andFEC groups were leukopenia and gastrointestinal toxicity, with a 5 year survival rate 88.7% in FPC and 85.7%in FEC group. Conclusions: FPC regimen is safe with superior long-term survival rate when compared withFEC, thus could be recommended as a postoperative chemotherapy regimen for Chinese patients with breastcancer.     

Adjuvant chemotherapy with doxorubicin and cyclophosphamide in women with rapidly proliferating node-negative breast cancer

This prospective clinical trial was designed to assess the impact of adjuvant chemotherapy in women with rapidly proliferating node-negative breast cancer. This group has been predicted to have a 5-year disease-free survival (DFS) of 70% without adjuvant chemotherapy. In this study, 449 women with rapidly proliferating breast cancer (91% measured by S-phase fraction and 9% by histochemistry) received adjuvant chemotherapy with doxorubicin/cyclophosphamide (AC) plus tamoxifen for estrogen receptor-positive or progesterone receptor-positive cancer. The 5-year DFS was 90% (+/- 2%) and the 5-year overall survival was 94% (+/- 1%). At a median follow-up of 62 months, the strategy of administering 6 cycles of AC to women with T2 N0 cancer and 3 cycles in those with smaller T1 N0 cancers appeared to eliminate tumor size as a potential prognostic factor. Adjuvant chemotherapy with AC appears effective in reducing recurrence rates for women with rapidly proliferating node-negative breast cancer.     

Cost-effectiveness analysis of adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) for node-positive breast cancer: modeling the downstream effects

Purpose BCIRG 001 demonstrated prolonged disease-free (DFS) and overall survival (OS) but increased toxicity for adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) versus 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) in women with node positive breast cancer (BC). This study evaluates quality-adjusted survival and cost-effectiveness of adjuvant TAC versus FAC, taking downstream decisions and events into account, including palliative chemotherapy with taxanes. Methods We developed a Markov model for a cohort of women with node positive BC eligible for adjuvant anthracyclines. Data input included clinical and resource utilization data collected prospectively from BCIRG 001. Treatment decisions and outcomes with disease recurrence were based on a systematic literature review with validity reviewed by a national panel of Canadian BC oncologists. Direct costs for resource utilization following Canadian practice patterns were included. Unit costs were obtained from provincial cost list and published drug list prices. Utility scores were derived from the literature. An incremental cost-effectiveness ratio (ICER) in cost per quality-adjusted life-years (QALY) gained for TAC versus FAC was calculated. Results For 1,000 women with node positive BC, the model showed that TAC would lead to a gain of 313 QALY (370 life years) at an additional cost of $5.8 Million Canadian dollars (Cdn) compared to FAC, over a 10-year time horizon. The ICER of TAC versus FAC was $18,505.54 Cdn per QALY gained. Sensitivity analyses supported the robustness of the model. By one-way sensitivity analyses of over 50 model variables, 95% of the cumulative ICER variation was from $6,000 to $28,000 Cdn/QALY. By multivariate Monte Carlo simulation, there was a 70% probability that the ICER would be under $50,000 CdN/QALY. Conclusion For women with node positive BC, TAC improves DFS and OS compared to FAC and is a cost-effective adjuvant chemotherapy strategy. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. An invited commentary to this article can be found at doi:.     

FAC (fluorouracil, doxorubicin, cyclophosphamide) as second line chemotherapy in patients with metastatic breast cancer progressing under FEC (fluorouracil, epirubicin, cyclophosphamide) chemotherapy

Background: The cross-over resistance between different anthracyclinesin breast carcinoma has not been largely evaluated in clinicaltrials. Patients and methods: Nineteen patients with metastatic breastcancer who had failed prior first line FEC chemotherapy (fluorouracil500 mg/m², epirubicin 50 mg/m² cyclophosphamide 500 mg/m², every4 weeks) were treated with a combination of fluorouracil 500mg/m², doxorubicin 50 mg/ m² and cyclophosphamide 500 mg/m²every 4 weeks (FAC). Results: Five patients achieved partial responses, ranging induration from 5 to 8 months. The main toxicity was cardiac,with congestive heart failure documented in five patients. Conclusion: The findings indicate an absence of cross-resistanceof doxorubicin in some epirubicin-resistant patients. breast cancer, anthracyclines, cross-resistance     

Dose-dense biweekly doxorubicin/docetaxel versus sequential neoadjuvant chemotherapy with doxorubicin/cyclophosphamide/docetaxel in operable breast cancer: second interim analysis

Timing of systemic treatment in primary operable breast cancer is subject to extensive investigation, suggesting that pathologic complete remission (pCR) might improve survival in this setting. The German Adjuvant Breast Cancer Group previously demonstrated the feasibility of a dose-dense biweekly schedule of 4 cycles doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 (ddAT) +/- tamoxifen in the neoadjuvant setting to yield a pCR of 9.7% (Gepardo trial). Patients assigned to ddAT received prophylactic granulocyte colony-stimulating factor support (5 micro g/kg days 5-10). The current study (GeparDUO) was designed to assess whether the pCR rate, including no viable invasive and preinvasive tumor cells, achieved with ddAT was equivalent to sequential administration of doxorubicin/cyclophosphamide followed by docetaxel (AC-DOC) over 24 weeks in primary operable breast cancer. From June 1999 to September 2001, 913 patients were enrolled in this trial. In total, 395 patients randomized before August 1, 2000, were included in the second interim analysis. Safety data were available from 369 patients (ddAT, n = 191; AC-DOC, n = 178) demonstrating that toxicity of both regimens was tolerable. Grade 3/4 neutropenia occurred in 39.8% of patients receiving ddAT and in 69.3% of patients treated with AC-DOC. Efficacy data were available in 378 patients. A pCR occurred in 14.8% of the primary breast tumors. According to the recommendations of the data monitoring committee, recruitment to the study was halted as of September 2001 (n = 913/1000) due to the significant difference in pCR rates observed between the treatment arms. Surgery was documented in 380 patients. Breast conservation was possible in 288 cases (75.8%). The application of both schedules is safe and feasible in an outpatient setting. Although, results obtained from this interim analysis are encouraging, caution is recommended until the results obtained show statistical difference in pCR.