Efficacy and Safety of Albumin-Bound Paclitaxel Compared to Docetaxel as Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer

BackgroundNanoparticle albumin-bound paclitaxel (nab-paclitaxel) as neoadjuvant chemotherapy (NAC) for breast cancer remains controversial. We conducted a retrospective study to compare the efficacy and safety of nab-paclitaxel with those of docetaxel as neoadjuvant regimens for HER2-negative breast cancer.MethodsIn this retrospective analysis, a total of 159 HER2-negative breast cancer patients who had undergone operation after NAC were consecutively analyzed from May 2016 to April 2018. Patients were classified into the nab-paclitaxel group (n = 79, nab-paclitaxel 260 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2) and the docetaxel group (n = 80, docetaxel 75 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2) according to the drug they received for neoadjuvant treatment. The efficacy and adverse events were evaluated in the two groups.ResultsThe pathological complete response (pCR)(ypT0/isN0) rate was significantly higher in the nab-paclitaxel group than in the docetaxel group (36.71% vs 20.00%; P = 0.031). The multivariate analysis revealed that therapeutic drugs, lymph node status, and tumor subtype were the most significant factor influencing treatment outcome. At a median follow-up of 47 months, disease-free survival (DFS) was not significantly different in those assigned to nab-paclitaxel compared with docetaxel (82.28% vs 76.25%; P = 0.331). The incidence of peripheral sensory neuropathy in the nab-paclitaxel group was higher than that in the docetaxel group (60.76% vs 36.25%; P = 0.008), while the incidence of arthralgia was observed more frequently in the docetaxel group (57.50% vs 39.97%; P = 0.047).ConclusionsCompared with docetaxel, nab-paclitaxel achieved a higher pCR rate, especially those patients with triple-negative breast cancer or lymph node negative breast cancer. However, there was no significant difference in DFS between the two groups. This study provides a valuable reference for the management of patients with HER2-negative breast cancer.

Confirmed three-year RFS and OS of the randomized trial of adjuvant S-1 versus S-1 plus docetaxel after curative resection of pStage III gastric cancer (JACCRO GC-07).

159 Background: JACCRO GC-07 is a randomized controlled trial to explore postoperative S-1/docetaxel compared to S-1 alone after D2 gastrectomy for pStage III gastric cancer (GC) patients. The second interim analysis demonstrated that the significant improvement of RFS was obtained by S-1/docetaxel compared to S-1 alone. The study was terminated by the recommendation of independent data and safety monitoring committee and the results were reported at ASCO 2018 and published in the Journal of Clinical Oncology (Yoshida K et al. 2019; 37:1296-1304). As 3 years have passed after completion of the enrollment, preplanned analysis was performed with the updated information of the patients. Methods: Patients with pStage III GC were randomly assigned to receive either S-1/docetaxel (S-1 80-120mg/body on days 1-14 with a 7-day rest followed by docetaxel 40mg/m2 on day 1 and S-1 80-120mg/body on days 1-14 every 21 days for 6 cycles followed by S-1 80-120mg/body on days 1-28 every 42 days for 4 cycles) or S-1 (80-120mg/body on days 1-28 every 42 days for 8 cycles) after D2 gastrectomy. Block randomization was performed by a central interactive computerized system stratified by the stage (IIIA, IIIB, IIIC) and histological type (differentiated or undifferentiated). The sample size of 1,100 was necessary to detect a 7% increase in the 3-year RFS. The primary endpoint was 3y RFS and the secondary endpoints were OS, TTF and safety. Results: In the present analysis, 400 recurrences and 324 deaths were confirmed among 912 patients during the median follow-up period of 42.5 months (0.3-85.16). The 3y RFS of 67.7% in the S-1/docetaxel group was significantly superior to 57.4% in the S-1 group (HR 0.715, 95% CI: 0.587-0.871, p = 0.0008) and the 3y OS was 77.7% in the S-1/docetaxel group and that of S-1 group was 71.2%, respectively (HR 0.742, 95% CI: 0.596-0.925, p = 0.0076), confirming the significant improving effect on the survival of the patient. Conclusions: Adjuvant S-1 plus docetaxel is recommended for patients with pStage III gastric cancer who underwent D2 gastrectomy without neoadjuvant chemotherapy. Clinical trial information: UMIN 000010337.

Differential Benefit of Adjuvant Docetaxel-Based Chemotherapy in Patients With Early Breast Cancer According to Baseline Body Mass Index

PURPOSE Lipophilic drugs, such as taxanes, have a high affinity for adipose tissue and a resulting higher volume of distribution. Here, we reanalyzed clinical trial data to investigate whether the efficacy of docetaxel-based chemotherapy differs from non-docetaxel–based chemotherapy in patients with breast cancer according to their baseline body mass index (BMI). PATIENTS AND METHODS We retrospectively analyzed data from all of the patients in the adjuvant BIG 2-98 trial (ClinicalTrials.gov identifier: NCT00174655 ; N = 2,887) comparing non-docetaxel– to docetaxel-containing chemotherapy. BMI (kg/m2) was categorized as follows: 18.5 to < 25, lean; 25 to < 30, overweight; and ≥ 30, obese. Disease-free survival (DFS) was the primary endpoint, and overall survival (OS) was the secondary endpoint. A second-order interaction was assessed among treatment, BMI, and estrogen receptor (ER) status. RESULTS There was no difference in DFS or OS according to BMI in the non-docetaxel group, while reduced DFS and OS were observed with increasing BMI category in the docetaxel group. Adjusted hazard ratios for DFS and OS were, respectively, 1.12 (95% CI, 0.98 to 1.50; P = .21) and 1.27 (95% CI, 1.01 to 1.60; P = .04) for overweight versus lean groups and were 1.32 (95% CI, 1.08 to 1.62; P = .007) and 1.63 (95% CI, 1.27 to 2.09; P < .001), respectively, for obese versus lean groups. Similar results were obtained when considering ER-negative and ER-positive tumors separately and when considering only patients who received a relative dose intensity ≥ 85% for docetaxel. A joint modifying role of BMI and ER status on treatment effect was evident for DFS (adjusted P = .06) and OS (adjusted P = .04). CONCLUSION This retrospective analysis of a large adjuvant trial highlights a differential response to docetaxel according to BMI, which calls for a body composition–based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer. These results now must be confirmed in additional series.

Propensity score matched comparison of docetaxel and androgen receptor axis-targeted (ARAT) agents in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate (IDC-P).

80 Background: Several studies have reported that intraductal carcinoma of the prostate (IDC-P) is a pathological adverse prognostic factor in patients with prostate cancer. However, the optimal treatment has not been established. The present study aimed to evaluate the efficacy of docetaxel and androgen receptor axis-targeted (ARAT) agents in patients with castration-resistant prostate cancer (CRPC) with IDC-P using a propensity score-matched analysis. Methods: We retrospectively identified 309 patients with CRPC from February 2007 to February 2016. They received initial androgen deprivation therapy (ADT) and after progression to CRPC, they received docetaxel or ARAT (abiraterone or enzalutamide) as the first-line life-prolonging therapy. The primary outcome of interest was OS from the time of CRPC diagnosis. We also investigated PFS from the time of docetaxel or ARAT initiation. Results: Propensity score-matching identified 85 patients in each group. There were no significant differences in patient characteristics between the groups. The median OS in the docetaxel group was 38.2 months versus 58.3 months in the ARAT group (HR 0.57; 95% CI 0.37–0.89; P =.01). Regarding patients with IDC-P, OS was significantly longer in the ARAT group than the docetaxel group (HR 0.48; 95% CI 0.26–0.86; P =.01), and there was no significant difference in each group, as in patients without IDC-P (HR 0.75; 95% CI 0.37–1.52; P =.43). The median PFS in the docetaxel group was 6.7 versus 7.8 months in the ARAT group (HR 0.65; 95% CI 0.45–0.94; P =.02). A multivariate analysis demonstrated that the presence of IDC-P, duration of primary ADT, visceral metastasis, and administration of ARAT as the first treatment for CRPC were independent prognostic factors for OS. Conclusions: Administration of ARAT as the first treatment for CRPC may prolong OS more than that of docetaxel, especially in patients with IDC-P.

Risk factors of grade ≥ 2 radiation pneumonitis after gemcitabine induction chemotherapy for patients with non-small cell lung cancer

Objectives To observe the risk factors affecting the occurrence of RP after gemcitabine-based induction chemotherapy. Methods Between January 2010 and December 2017, patients with NSCLC received gemcitabine or docetaxel chemotherapy, followed by radiotherapy at Zhejiang cancer hospital were enrolled in this study. Patients were treated with gemcitabine or docetaxel induction chemotherapy, followed by radiotherapy or concurrent chemoradiotherapy. Acute radiation pneumonitis was scored post chemoradiotherapy. Results One hundred and eighty-four patients with NSCLC were included in the gemcitabine group and 144 in the docetaxel group. The gemcitabine group experienced a higher incidence of grade ≥ 2 RP, compared with docetaxel group (25.5% Vs. 13.2%, P = 0.005). The optimal cutoff values of lung V5, V20, V30 and MLD were set at 44% (AUC [area under the curve] = 0.593), 24% (AUC = 0.607), 14.2% (AUC = 0.622) and 1226 cGy (AUC = 0.626). On multivariate analysis, only lung V30 was identified as a predictor for grade ≥ 2 RP (P = 0.03). The grade ≥ 2 RP rate was only 9.4% for the low-risk group (Lung V5 ≤ 44%, V20 ≤ 24%, V30 ≤ 14.2%, and MLD ≤ 1226 cGy) in patients received gemcitabine induction chemotherapy. Conclusions Gemcitabine chemotherapy before thoracic radiotherapy in NSCLC patients was related to a higher incidence of grade ≥ 2 RP, compared with docetaxel chemotherapy. The Lung dose-volume variable V30 was the best predictor of grade ≥ 2 RP.

Effects of Pemetrexed and Docetaxel Combined with Cisplatin in the Treatment of Non-Small Cell Lung Cancer

Purpose: To compare the clinical effects of pemetrexed and docetaxel combined with cisplatin in the treatment of patients with non-small cell lung cancer. Methods: A total of 58 patients with non-small cell lung cancer who were enrolled between January 2017 and January 2018 were enlisted into a randomized digital table. Twenty-nine patients who have received treatment with combined pemetrexed and cisplatin were assigned to the pemetrexed group whereas for the other 29 patients which were treated with docetaxel and cisplatin combined, were assigned to the docetaxel group to verify the calculated clinical treatment efficiency of the patients with non-small cell lung cancer, SVCAM-1 and alCAM-1 concentrations and to evaluate the quality of life scores of the patients after half a year as well as the incidences of adverse reactions following the treatments provided. Results: The differences in SVCAM-1 and alCAM-1 concentrations, and incidence of adverse reactions in patients with non-small cell lung cancer in the docetaxel group as compared with patients in the pemetrexed group after the treatments were statistically significant (P<0.05) where the calculations were performed with data sets gathered from and between the two groups. Additionally, SVCAM-1 and alCAM-1 concentrations in patients in both pemetrexed group and docetaxel group demonstrated significant differences in concentrations before and after the treatments were provided, P<0.05. The comparative studies of the effects of the treatments on the quality of life scores and clinical treatment efficiency between the two groups after half a year, P>0.05, demonstrated no analytical significance. Conclusion: Both pemetrexed combined with cisplatin and docetaxel in combination with cisplatin as forms of treatments demonstrated significant effects in patients with non-small cell lung cancer. However, based on our study, it was found that the combined treatment involving pemetrexed and cisplatin can further reduce adverse reactions and thus, is worthy of clinical application.Â

Safety and efficacy of abiraterone acetate (AA) in patients aged 75 or more with metastatic castration-resistant prostate cancer (mCRPC) in both pre-chemotherapy or post-chemotherapy settings: Real-life experience from thirteen Italian centers.

209 Background: Prostate cancer affects mainly elderly patients (pts) that have different comorbidities. AA is a selective androgen synthesis inhibitor that showed the efficacy in either chemotherapy (CT) naive pts or those pretreated with docetaxel. Its oral administration and good tolerability make it a manegeable treatment for elderly mCRPC pts. Methods: We collected retrospectively data regarding mCRPC pts aged ≥75 years treated with AA in 13 Italian Centers since April 2013. The median age was 79 years (r. 75-90) with 48% of pts being octagerians. Post CT pts had more extensive disease, higher baseline PSA and ECOG PS. Nearly all the pts had comorbidities, the most frequent being hypertension present in 146 pts (58%), 43 pts (17%) had diabetes type II. We evaluated duration of the AA treatment, overall response rate (ORR), 50% PSA decline, time to progression (TTP) and overall survival (OS). We reported all toxicities observed. Results: A total of 252 pts ,147 pre treated with docetaxel and 105 chemo naive, were included. Median duration of treatment with AA was 8,6 months in post CT and 11,5 in CT naive pts. ORR was 35,3% in pre docetaxel and 27,4% in post docetaxel group. 64 pts (65%) and 51 pts (46%) obtained 50% PSA reduction in pre and post docetaxel group, respectively. Median TTP was 8,6 in post docetaxel and 11,9 in CT naive pts. We observed a median OS of 13,8 months in post CT group while for CT naive pts data were not yet mature. AA was well tolerated with only 8 pts (3,2%) who discontinued treatment due to toxicity, while in 4 pts (1,6%) temporary dose reductions were performed. The most frequent G3 toxicities were hypertension and liver toxicity with 4 pts (1,6%) and 5 pts (2%), respectively. After progressing on AA, 85 pts (34%) received at least one subsequent treatment. 40 pts (15,9%) are still on treatment with AA. Conclusions: Even if almost all the pts reported comorbidities at AA start and 72 pts (28,6%) had PS ECOG 2, only a small proportion of them discontinued the treatment due to toxicity confirming that AA is well tolerated and efficient treatment also for elderly patients.

Chronic neuropathic pain following oxaliplatin and docetaxel: A 5-year follow-up questionnaire study

BackgroundAdjuvant chemotherapy with docetaxel and oxaliplatin increases survival in patients with high-risk breast and colorectal cancer, respectively, but may induce acute and chronic neurotoxicity. This study is a 5-year follow-up of chronic chemotherapy-induced peripheral neuropathy (CIPN).MethodsIn 2011–2012, 74 patients with high-risk colorectal cancer and 100 patients with high-risk breast cancer answered a questionnaire before, during and one year after receiving adjuvant chemotherapy with oxaliplatin and docetaxel, respectively. In 2016, a 5-year follow-up with the same questionnaire was performed in survivors.ResultsFifty-two (36.5% women) of 74 patients (91%) treated with oxaliplatin and 80 (100% women) of 100 patients (85%) treated with docetaxel answered the questionnaire. The most common symptoms of CIPN were tingling in the hands (44.2% in the oxaliplatin (CI 95% 30.5; 58.7) and 36.3% in the docetaxel group (CI 95% 25.8; 47.8)) and feet (52.0% in the oxaliplatin (CI 95% 37.6; 66.0) and 37.5% (CI 95% 29.9; 49.0) in the docetaxel group) and numbness in the feet (34.6% in the oxaliplatin (CI 95% 22.0; 49.1) and 17.5% (CI 95% 9.9; 27.6) in the docetaxel group). Pain was present in the hands or feet in 28.9% of patients treated with oxaliplatin (CI 95% 17.12; 43.0) and 31.3% of patients treated with docetaxel (CI 95% 21.3; 42.6).ConclusionsThe results showed no major change in symptoms of neuropathy or pain from 1 to 5 years after chemotherapy. Symptoms of neuropathy were more common in patients treated with oxaliplatin.

A Difference in the Incidences of Hypersensitivity Reactions to Original and Generic Taxanes

Purpose: To compare incidences of hypersensitivity reaction (HSR) between original and generic taxanes including paclitaxel and docetaxel. Methods: We conducted a prospective study enrolling all patients receiving taxanes at King Chulalongkorn Memorial Hospital. Taxanes were infused accordingly to the step-wise rate escalation protocol at this hospital. Active surveillance for HSRs was performed. During the study period, there was only 1 generic brand used for each taxane. We primarily compared the incidences of HSR between original and generic drugs for each taxane. Results: During the period from January 1 to December 31, 2013, a total of 258 consecutive patients receiving taxanes were enrolled; 128 received paclitaxel, i.e. 65 and 63 in the original (Taxol) and generic arms, respectively, and 130 received docetaxel, i.e. 66 and 64 in the original (Taxotere) and generic arms, respectively. Premedication, including antihistamines and dexamethasone, was administered to all patients 30 min before taxane infusion. There were 26 (10.0%) HSR events including 24 grade 2 and 2 grade 3 HSRs. In the paclitaxel group, there were 9 (13.8%) and 7 (11.1%) HSRs in the original and generic arms, respectively (p = 0.791). In the docetaxel group, there were 9 (13.6%) and 1 (1.6%) HSRs in the original and generic arms, respectively (p = 0.017). No life-threatening symptoms or permanent discontinuation of taxanes occurred. Conclusions: In this prospective study, the incidences of HSR were similar with generic and original paclitaxel but significantly different with generic and original docetaxel.

A randomized phase II trial comparing continuation maintenance therapy with pemetrexed and switch maintenance therapy with docetaxel after first-line therapy with carboplatin and pemetrexed in patients with advanced nonsquamous non-small cell lung cancer.

8038 Background: Emerging evidence suggests that maintenance chemotherapy could prolong survival in patients with advanced non-small-cell lung cancer (NSCLC), whereas the optimal treatment strategy remains controversial. Methods: We conducted a randomized phase II study to compare the efficacy and safety of continuation maintenance with pemetrexed (500 mg/m2) and switch maintenance with docetaxel (60 mg/m2) in patients with non-squamous NSCLC who achieved disease control after first-line chemotherapy with four cycles of carboplatin (AUC 6) and pemetrexed (500 mg/m2). Results: Eighty-five patients participated in the study, and 26 and 25 patients were randomized to the pemetrexed and the docetaxel maintenance therapies, respectively. The docetaxel group showed a trend toward longer progression-free survival (median 8.2 months, 95% CI; 3.9-12.2 months) compared with the pemetrexed group (median 4.1 months, 95% CI; 3.0-6.1 months), but not significantly (log-rank p=0.084). Grade 3/4 hematologic toxicity was significantly more frequent in the docetaxel group (80%) than the pemetrexed group (20%, p<0.0001). Conclusions: Continuation maintenance with pemetrexed after induction therapy with carboplatin and pemetrexed may be an efficacious treatment with less toxicity. In contrast, switch maintenance with docetaxel frequently causes severe hematologic toxicity but may be more efficacious. Further studies are warranted to evaluate the risks and benefits of maintenance therapies. Clinical trial information: 000004075.