小金片联合NX方案治疗紫杉类及蒽环类耐药晚期乳腺癌的临床研究

目的 观察小金片联合NX化疗方案(长春瑞滨联合卡培他滨)治疗紫杉类及蒽环类耐药晚期乳腺癌的临床效果.方法 选取2019年1月—2020年1月南阳市第二人民医院收治的100例紫杉类及蒽环类耐药晚期乳腺癌患者,根据信封抽签法分为对照组和治疗组,每组各50例.对照组给予NX化疗方案治疗,第1、8天静脉滴注酒石酸长春瑞滨注射液...     

Effect of taxane‐based neoadjuvant chemotherapy on fibroglandular tissue volume and percent breast density in the contralateral normal breast evaluated by 3T MR

The aim of this study was to evaluate the change of breast density in the normal breast of patients receiving neoadjuvant chemotherapy (NAC). Forty‐four breast cancer patients were studied. MRI acquisition was performed before treatment (baseline), and 4 and 12 weeks after treatment. A computer‐algorithm‐based program was used to segment breast tissue and calculate breast volume (BV), fibroglandular tissue volume (FV), and percent density (PD) (the ratio of FV over BV × 100%). The reduction of FV and PD after treatment was compared with baseline using paired t‐tests with a Bonferroni–Holm correction. The association of density reduction with age was analyzed. FV and PD after NAC showed significant decreases compared with the baseline. FV was 110.0 ml (67.2, 189.8) (geometric mean (interquartile range)) at baseline, 104.3 ml (66.6, 164.4) after 4 weeks (p < 0.0001), and 94.7 ml (60.2, 144.4) after 12 weeks (comparison with baseline, p < 0.0001; comparison with 4 weeks, p = 0.016). PD was 11.2% (6.4, 22.4) at baseline, 10.6% (6.6, 20.3) after 4 weeks (p < 0.0001), and 9.7% (6.2, 17.9) after 12 weeks (comparison with baseline, p = 0.0001; comparison with 4 weeks, p = 0.018). Younger patients tended to show a higher density reduction, but overall correlation with age was only moderate (r = 0.28 for FV, p = 0.07, and r = 0.52 for PD, p = 0.0003). Our study showed that breast density measured from MR images acquired at 3T MR can be accurately quantified using a robust computer‐aided algorithm based on non‐parametric non‐uniformity normalization (N3) and an adaptive fuzzy C‐means algorithm. Similar to doxorubicin and cyclophosphamide regimens, the taxane‐based NAC regimen also caused density atrophy in the normal breast and showed reduction in FV and PD. The effect of breast density reduction was age related and duration related. Copyright © 2013 John Wiley & Sons, Ltd.     

Clinical Implications of HER-2 and P53 in Taxane-Based and Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer

Objective  To evaluate the predictive value of human epidermal growth factor receptor-2 (HER-2) and P53 in taxanebased and anthracycline-based neoadjuvant chemotherapy (NAC) in breast cancer. Methods  Sixty-two patients with breast cancer were included in this study. Twenty-two patients were treated with taxane-based (taxane group) and 40 with anthracycline-based (anthracycline group). ER, PR, c-erbB2 and P53 were detected by immunohistochemistry staining before NAC, and Fluorescence In Situ Hybridization(FISH) was used to detect the HER-2 gene amplification for the cases with the expression of c-erbB2 protein as (++) or (+++). The efficacy of the regimens was evaluated a er NAC. Results  In the anthracycline group, objective response (OR) was observed in 30 out of 40 patients (75%), whereas no response (NR) was observed in 10 patients (25%). In the taxane group, OR was observed in 15 patients out of 22 patients (68.2%), whereas NR was observed in 7 patients (31.8%). HER-2-negative status was correlated with a high OR in both taxane-based and anthracycline-based NAC (P = 0.023 and P = 0.029), whereas P53-negative status was correlated with high OR rate in anthracycline-based NAC (P = 0.041). The significant difference of the CR rates was observed between the patients took < 4 cycles and ≥ 4 cycles NAC (4.65% vs. 21.05%, P < 0.05). Conclusion  The patients with HER-2 gene non-amplication may be sensitive to both taxane-based and anthracycline-based chemotherapy; the patients without P53 overexpression may suitable to select anthracycline-based chemotherapy; and proper increased NAC cycles may increase CR rates. This work was supported by a grant from the Ministry of Public Health Scientific Research Foundation of China (No.WKJ2007-3-001).     

Phase I/II study of DHA-paclitaxel in combination with carboplatin in patients with advanced malignant solid tumours

DHA-paclitaxel is a conjugate of paclitaxel and the fatty acid, docosahexaenoic acid. Preclinical studies have demonstrated increased activity, relative to paclitaxel, with the potential for an improved therapeutic ratio. We conducted a phase I study to determine the maximum tolerated doses of DHA-paclitaxel and carboplatin when administered in combination. Two cohorts of patients were treated: carboplatin AUC 5 with DHA-paclitaxel 660 mg m(-2) and carboplatin AUC 5 with DHA-paclitaxel 880 mg m(-2). Both drugs were given on day 1 every 21 days. A total of 15 patients were enrolled with a median age of 59 years (range 33-71). All patients had advanced cancer refractory to standard treatment, performance status 0-2 and were without major organ dysfunction. A total of 54 cycles of treatment were delivered. No dose-limiting toxicity (DLT) was seen in the first cohort of three patients. In an expanded second cohort, neutropenia was the main DLT, occurring in the first cycle of treatment in five of 12 patients: three of these patients and one additional patient also experienced dose-limiting grade 3 transient rises in liver transaminases. No alopecia was seen and one patient developed clinically significant neuropathy. One partial response was seen in a patient with advanced adenocarcinoma of the oesophago-gastric junction and 12 patients had stable disease with a median time to progression of 184 days (range 60-506 days). The recommended phase II dose in pretreated patients is Carboplatin AUC 5 and DHA-paclitaxel 660 mg m(-2) given every 21 days. Further studies with Carboplatin AUC 5 and DHA-paclitaxel 880 mg m(-2), given every 28 days, are warranted in chemo-naive patients.     

Phase I trial of the novel taxane BMS-184476 administered in combination with carboplatin every 21 days

The aim of the study was to determine the maximum-tolerated dose and dose-limiting toxicities for BMS-184476, in combination with carboplatin, in patients with advanced solid tumours and to describe any preliminary antitumour activity associated with this regimen. Patients received combination therapy with BMS-184476 given intravenously over 1 h followed by carboplatin administered over 30 min on day 1 of a 21-day cycle. In all, 28 patients received 146 cycles of BMS-184476 and carboplatin. Patients were enrolled at four dose levels: BMS-184476 (mg m(-2))/carboplatin (mg min ml(-1)): 40/5, 50/5, 50/6 and 60/6. Dose-limiting toxicity at 60/6 was neutropenia. Among 27 evaluable patients, 11 demonstrated stable disease for a median of 8.5 cycles. In 22 patients, the pharmacokinetics of BMS-184476 appeared independent of dose of BMS-184476. The mean+/-s.e.m. values for clearance (Cl), volume of distribution at steady state and apparent terminal half-life of BMS-184476 in the four dose groups during cycle 1 were 192+/-25 ml min m(-2), 377+/-69 l m(-2) and 33.7+/-5.9 h, respectively. An increase in the dose of carboplatin from 5 to 6 mg min ml(-1) may have decreased Cl of BMS-184476. BMS-184476 in combination with carboplatin was well tolerated at a dose of 50/6 and shows evidence of antitumour activity in a pretreated population.     

Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate

Docetaxel (Taxotere), alone or in combination with other anticancer agents, has proven efficacy in the first- and second-line treatment of metastatic breast cancer. This phase II study investigated the efficacy and tolerability of docetaxel as neoadjuvant chemotherapy in women with stage II-III primary operable breast cancer. Patients (n=88) were treated with six cycles of docetaxel at 100 mg m(-2) every 21 days, followed by definitive surgery and radiotherapy. After six cycles of docetaxel, the overall clinical response rate was 68.4% (CI 95%: 58.1-78.7%), including 19.0% complete remissions. Breast conservation was achieved in 72.4% of patients. A high pathological complete response (pCR) rate in breast was confirmed in 15 patients (19.8% (CI 95%: 10.8-28.8%)) on Chevallier's classification restricted to breast and in 27 patients (35.5% (CI 95%: 24.7-46.3%)) on Sataloff's classification. After a median follow-up of 30.8 months, 19 recurrences were documented with a median time to first recurrence of 17.3 months. Patients with stage III tumours had more recurrences than patients with stage II tumours (P=0.02). The principal toxicity of docetaxel is myelosuppression and 70.5% of patients developed grade III or IV neutropenia with 13.6% developing neutropenic sepsis. There was no case of severe cardiac toxicity, thrombocytopenia or any other serious adverse events. In conclusion, neoadjuvant docetaxel induces a high pCR and breast-conservation rate. Docetaxel monotherapy is a highly effective regimen that merits formal comparison with currently used combination regimens in a randomised phase III study.     

Serum micronutrients and prealbumin during development and recovery of chemotherapy‐induced peripheral neuropathy

Chemotherapy‐induced peripheral neuropathy (CIPN) is a frequent adverse event. Nutritional status can become impaired in cancer patients, potentially contributing to neuropathy's evolution. Our aim was to evaluate serum micronutrients and prealbumin in a cohort of 113 solid‐cancer patients receiving platinum and taxane compounds during the development and recovery of neuropathy, up to 1 year after finishing treatment. CIPN was graded according to Total Neuropathy Score^© and NCI.CTCv3 at T0 (baseline), T1 (1–3 months), and T12 (12 months) after chemotherapy. CIPN was classified as asymptomatic (< grade 2) or symptomatic (≥2). CIPN recovery was defined as ≥1 grade improvement at T12. Symptomatic CIPN developed in 52% of patients. Symptomatic patients presented a higher increase in TNSc (p < 0.001), in TNSr^© (p < 0.001), and decrease in sural (p < 0.001) and radial nerve conduction (p < 0.001). No significant differences with any of the micronutrients were observed along T0‐T1 period between severity or chemotherapy groups. By T12, symptomatic patients without recovery had a decrease in vitamin E levels (p = 0.019) and prealbumin (p = 0.062) compared with those symptomatic that improved. A correlation between the variation of vitamin E and prealbumin at T0‐T1 (r = 0.626, p = 0.001) and T1‐T12 (r = 0.411, p = 0.06) was observed. After chemotherapy treatment, the improvement of patients displaying symptomatic neuropathy is related to vitamin E and prealbumin serum levels. Our results suggest that nutritional status can play a role in CIPN recovery.