Effect of Epirubicin Plus Paclitaxel vs Epirubicin and Cyclophosphamide Followed by Paclitaxel on Disease-Free Survival Among Patients With Operable ERBB2-Negative and Lymph Node-Positive Breast Cancer: A Randomized Clinical Trial.

Importance: Adjuvant therapy is an important and effective treatment for breast cancer. However, there is a lack of head-to-head clinical trials comparing the regimens epirubicin plus paclitaxel (EP) vs epirubicin and cyclophosphamide followed by paclitaxel (EC-P) in breast cancer. Objective: To evaluate the noninferiority of a cyclophosphamide-free (EP) regimen compared with the standard EC-P regimen for patients with operable hormone receptor-positive, ERBB2 (formerly HER2)-negative, lymph node-positive breast cancer. Design, Setting, and Participants: This prospective, open-label, phase 3, noninferiority randomized clinical trial was conducted from June 1, 2010, to June 30, 2016, in the Cancer Hospital, Chinese Academy of Medical Sciences, Beijing. Patients with hormone receptor-positive, ERBB2-negative, lymph node-positive operable breast cancer were included and randomized into 2 treatment groups. Data were analyzed from June 30, 2016, to November 1, 2022. Interventions: Patients received adjuvant epirubicin (75 mg/m2) and paclitaxel (175 mg/m2) every 3 weeks for 6 cycles (EP regimen) or epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks for 4 cycles followed by paclitaxel (175 mg/m2) every 3 weeks for 4 cycles (EC-P regimen) as the intention-to-treat (ITT) population. Main Outcomes and Measures: The primary outcome was disease-free survival (DFS), and the secondary outcomes included overall survival (OS), distant DFS, and safety. Results: A total of 900 patients were registered, and 813 eligible patients (median age, 48 [IQR, 41-56] years) were randomly assigned to the EP group (n = 407) or the EC-P group (n = 406) after the surgical procedure. Through a median follow-up of 93.6 (IQR, 60.9-114.1) months, the hazard ratio (HR) of DFS for EP vs EC-P was 0.82 (95% CI, 0.62-1.10; 5-year DFS, 86.0% vs 80.6%; noninferior P = .001). The 5-year OS for the ITT population treated with the EP or the EC-P regimen was 94.7% vs 95.0%, respectively (HR, 0.95 [95% CI, 0.61-1.49]). Patients in the EP group had more frequent toxic effect events than those in the EC-P group. Conclusions and Relevance: In this prospective, open-label, phase 3, randomized clinical trial, the EP regimen was noninferior to the EC-P regimen. These findings supported that the EP regimen could be an effective adjuvant chemotherapy regimen for women with ERBB2-negative breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT01134523.

A Prospective, Randomized, Placebo-Controlled Study Assessing the Efficacy of Chinese Herbal Medicine (Huangqi Guizhi Wuwu Decoction) in the Treatment of Albumin-Bound Paclitaxel-Induced Peripheral Neuropathy.

Objective: This study aimed to evaluate the efficacy and safety of Huangqi Guizhi Wuwu decoction (HGWD), which is composed of five crude drugs (Astragali Radix, Cinnamomi Ramulus, Paeoniae Radix Alba, Zingiberis Rhizoma Recens, and Jujubae Fructus), in the treatment of albumin-bound paclitaxel (nab-PTX)-induced peripheral neuropathy (PN) in Chinese patients with breast cancer (BC). Methods: This trial was conducted at the National Cancer Center in China from January 2020 to June 2022. The eligible participants were assigned randomly in a 1:1 ratio to an HGWD group or a control group. The outcome measure was EORTC QLQ-CIPN20 questionnaire. Results: 92 patients diagnosed with BC were enrolled and randomized to either HGWD group (n = 46) or control group (n = 46). There were no significant differences in baseline characteristics between the two groups (p > 0.05). A statistical analysis of the sensory and motor functions of the EORTC QLQ-CIPN20 scores showed that patients in the HGWD group reported a larger decrease in CIPN sensory scores than those in the control group (p < 0.001). The EORTC QLQ-CIPN20 autonomic scores showed no statistical significance between the two groups (p > 0.05). Conclusions: HGWD packs could significantly improve patients' nab-PTX-induced PN, increase the tolerance for nab-PTX-containing chemotherapy, and further improve the quality of life of patients with BC.

CACA Guidelines for Holistic Integrative Management of Breast Cancer.

Purpose: Breast cancer is now the most common malignant tumor worldwide. About one-fourth of female cancer patients all over the world suffer from breast cancer. And about one in six female cancer deaths worldwide is caused by breast cancer. In terms of absolute numbers of cases and deaths, China ranks first in the world. The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China. Methods: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to classify evidence and consensus. Results: The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer, breast cancer screening, breast cancer diagnosis, early breast cancer treatment, advanced breast cancer treatment, follow-up, rehabilitation, and traditional Chinese medicine treatment of breast cancer patients. Conclusion: We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

Switching to anastrozole plus goserelin vs continued tamoxifen for adjuvant therapy of premenopausal early-stage breast cancer: preliminary results from a randomized trial.

PURPOSE: To assess the efficacy, safety, and quality-of-life impact of switching adjuvant treatment in hormone receptor-positive primary breast cancer patients who are still premenopausal after 2-3 years of tamoxifen therapy to anastrozole plus goserelin as compared with continuing tamoxifen over a total period of 5 years. PATIENTS AND METHODS: Hormone receptor-positive, premenopausal, lymph node-positive, or tumor size ≥4 cm breast cancer patients who had received tamoxifen for 2-3 years were randomly assigned to continue tamoxifen treatment (TAM group) or switch to adjuvant anastrozole plus goserelin (ADD group) and continue treatment for another 2-3 years (total treatment duration 5 years). Endpoints evaluated were adverse events (AEs), changes in bone mineral density, quality of life, and disease-free survival-related events. RESULTS: A total of 62 patients (33 in the ADD group and 29 in the TAM group) were evaluated. Grade 3-4 drug-related AEs occurred in five patients (15.2%) in the ADD group vs none in the TAM group. In the ADD group, arthralgias were the most common AEs (5/33 patients; 15.2%), and three patients in this group were discontinued because of AEs. Treatment was temporarily suspended due to AEs in three patients (9.1%) in the ADD group and one patient (3.4%) in the TAM group. Compared with continuing TAM therapy, switching to anastrozole plus goserelin did not result in any worsening of bone mineral density or quality of life. During a median follow-up of 34 months, five patients (15.2%) in the ADD group had disease-free survival events vs four patients (13.8%) in the TAM group. CONCLUSION: For early-stage breast cancer patients who remain premenopausal following 2-3 years of adjuvant tamoxifen therapy, switching to anastrozole plus goserelin therapy was safe with tolerable adverse effects. However, it did not show superior efficacy compared to remaining on tamoxifen treatment. TRIAL REGISTRATION: ClinicalTrials.gov (identifier NCT01352091).

Timing of paclitaxel treatment in pre-operative or post-operative does not affect survival in breast cancer patients.

BACKGROUND: Two epirubicin and paclitaxel-based neoadjuvant chemotherapy regimens were compared in breast cancer patients. METHODS: We enrolled 309 breast cancer patients who received two types of regimens: cyclophosphamide + epirubicin dose-dense neoadjuvant chemotherapy followed by sequential postoperative paclitaxel single-drug medication, and paclitaxel + epirubicin standard neoadjuvant chemotherapy followed by two cycles of the same chemotherapy after surgery. The primary endpoint was a pathological complete response (pCR) and the secondary endpoints were disease-free and overall survival. RESULTS: The median follow-up time was 65 months. The overall pCRs for pathological efficacy and efficacy of primary lesions were 14.4% and 29.3%, respectively (P < 0.001). The pCR of the paclitaxel + epirubicin group was significantly higher than in the cyclophosphamide + epirubicin group (17.3% vs. 9.2%; P = 0.0345), but the five-year disease-free survival rates in both groups were not significantly different (82.9% vs. 75.3%; P = 0.916). CONCLUSIONS: The results of our study indicated that the timing of paclitaxel therapy, either preoperative or postoperative, does not affect survival times in breast cancer patients.

[Impact of glutamine, eicosapntemacnioc acid, branched-chain amino acid supplements on nutritional status and treatment compliance of esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy].

OBJECTIVE: To explore the effects of glutamine, eicosapntemacnioc acid (EPA) and branched-chain amino acids supplements in esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy. METHODS: From April 2013 to April 2014, a total of 104 esophageal and gastric carcinoma patients on chemotherapy or concurrent chemoradiotherapy were recruited and randomly divided into experimental and control groups. Both groups received dietary counseling and routine nutritional supports while only experimental group received supplements of glutamine (20 g/d), EPA (3.3 g/d) and branched-chain amino acids (8 g/d). And body compositions, blood indicators, incidence of complications and completion rates of therapy were compared between two groups. RESULTS: After treatment, free fat mass and muscle weight increased significantly in experiment group while decreased in control group (P < 0.05). And albumin, red blood cell count, white blood cell count and blood platelet count remained stable in experiment group while declined significantly in control group. During treatment, compared to control group, the incidences of infection-associated complication were lower (6% vs 19%, P < 0.05) and the completion rates of therapy were significantly higher in experiment group (96% vs 83%, P < 0.05). CONCLUSION: Supplements of glutamine, EPA and branched-chain amino acids can help maintain nutrition status, decrease the complications and improve compliance for esophageal cancer patients on concurrent chemo-radiotherapy and gastric cancer patients on postoperative adjuvant chemotherapy.

A pooled analysis of gemcitabine plus docetaxel versus capecitabine plus docetaxel in metastatic breast cancer.

In two randomized phase III trials of patients with metastatic breast cancer (MBC), gemcitabine-docetaxel (GD) and capecitabine-docetaxel (CD) had similar efficacy, but distinct safety profiles. Methods. Data from two GD versus CD studies were pooled; overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) were determined. Cox proportional hazards models identified prognostic factors associated with improved OS and PFS. Using a multivariate prognostic model incorporating identified adverse prognostic factors, we grouped MBC patients into low-, intermediate-, and high-risk categories. Hazard ratios (HRs) of GD over CD for OS and PFS were determined for subsets of patients. Results. Baseline demographics of the pooled population were mostly well balanced. In the pooled population, there were no significant differences between GD versus CD for OS (HR = 1.02; p = .824), PFS (HR = 1.15; p = .079), and ORR (p = .526). In the pooled crossover population, there were trends toward improved OS (HR = 0.82; p = .171) and PFS (HR = 0.93; p = .557) with GD. Several prognostic factors (including prior adjuvant taxane) for improved OS or PFS were identified; however, there were no significant interactions between treatment arms and prognostic factors for PFS or OS, except number of metastatic sites. In the prognostic model, median OS and PFS were numerically lower in the high-risk group versus the intermediate- and low-risk groups. Conclusion. This analysis confirms the lack of efficacy difference between GD and CD in the pooled population, crossover population, and almost all subpopulations. Several prognostic factors were associated with improved outcomes in the pooled population.

Ixabepilone plus capecitabine for Chinese patients with metastatic breast cancer progressing after anthracycline and taxane treatment.

PURPOSE: Effective treatment options for patients with metastatic breast cancer pretreated with or resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed as a prospective clinical trial to evaluate the efficacy and safety of ixabepilone plus capecitabine in both anthracycline-pretreated and resistant and taxane-resistant metastatic breast cancer of Chinese women. PATIENTS AND METHODS: Patients with measurable disease who had anthracycline and taxanes as prior neoadjuvant, adjuvant or metastatic therapy were treated with ixabepilone at 40 mg/m(2) intravenously on day 1 of 21-day cycle plus capecitabine 2,000 mg/m(2) orally on day 1 through 14 of a 21-day cycle. The primary end point was the objective response rate. The secondary end points were time to progression, overall survival, and toxicity profiles. RESULTS: Twenty-one patients received 146 cycles with a median of 5 cycles (range 1-13 cycles) per patients. Fourteen patients (66.7%) had partial response, 5 patients (23.8%) had stable disease, and 2 patients (9.5%) had progressive disease. Median time to progression and duration of response were 6.2 and 6.0 months, respectively. The median overall survival was 16.7 months. Eight (38.1%) patients required dose reduction and 14 (66.7%) patients discontinued treatment for adverse effect. Grade 3/4 treatment-related events included fatigue (28.6%), peripheral sensory neuropathy (33.3%), neutropenia (61.9%), anemia (4.7%), hypokalemia (4.7%), hand and foot syndrome (19.0%) and infection (9.5%). Resolution of grade 3/4 peripheral neuropathy was reversible after a median period of 6 weeks. CONCLUSION: Ixabepilone plus capecitabine demonstrated a clear activity and an acceptable safety profile in Chinese patients with anthracycline-pretreated/resistant and taxane-resistant metastatic breast cancer, and the majority of patients completed 6 cycles of the therapy with manageable neuropathy toxicities.

[Results of combined therapy for 1260 patients with small cell lung cancer].

OBJECTIVE: To evaluate the efficacy of combined modality treatment and determine the prognostic factors for small cell lung cancer (SCLC). METHODS: From January 1974 to December 1995, 1260 patients with SCLC treated were retrospectively evaluated, with limited lesions in 732 patients, extensive lesions in 500 and stage unrecorded in 28. 553 patients were alloted into chemotherapy + radiotherapy (C + R) group, 355 into C + R + C group, 97 into R + C group, 126 into C group, 64 into R group and 65 into surgery (S + C + R) group. Patients with limited lesions received 2 - 4 cycles of chemotherapy including COMC, COMP, COMVP and CE-CAP. Radiotherapy was given to a dose of 40 - 70 Gy/4 - 7 w. Radiation portals for patients with limited lesions encompassed the primary tumor, hilar lymphatic drainage areas, partial mediastinum and bilateral supraclavicular regions. Patients with extensive lesions mainly received chemotherapy with or without palliative irradiation. RESULTS: The overall CR and PR rates were 26.7% and 52.3%. Local recurrence and distant metastasis rates were 58.8% and 61.5%. The 1-, 3- and 5-year survival rates were 50.2%, 14.7% and 11.7%, with median survival time of 12 months. The era, sex, age, tumor stage and treatment modality were all significant prognostic factors by both uni-variate and multi-variate analyses (P < 0.05). The result of S + C + R rated the best among these modalities and the result of C + R + C was superior to C + R, though the difference of which was not significant. CONCLUSION: Surgical resection should be considered as one part of comprehensive therapy for small cell lung cancer patients with limited lesions whenever possible. On top of routine chemotherapy early administration of radiotherapy is advisable.