taxane and Hand-Foot-Syndrome

Capecitabine is frequently used alone or combined with other chemotherapy agents for the treatment of metastatic breast cancer in relapsed patients.. The objective of this meta-analysis is to evaluate the effectiveness and safety of capecitabine monotherapy versus combination in the treatment of metastatic breast cancer patients pretreated with anthracycline and taxane.. Eligible randomized controlled trials examining the efficacy and safety of capecitabine alone compared to capecitabine combination were systematically searched. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grades 3-4 drug-related adverse events were the outcomes assessed.. A total of 6,714 patients of 9 trials were involved in the pooled analysis. Our findings demonstrated that capecitabine combination is significantly superior to capecitabine monotherapy in improving PFS (hazard ratio [HR] 1.32, 95% CI 1.13-1.54, p < 0.0001) and ORR (risk ratio [RR] 0.67, 95% CI 0.54-0.83, p < 0.001), but it was insignificant in OS (HR 1.09, 95% CI 0.98-1.22, p = 0.12). On the other hand, the incidence of non-hematological adverse events such as hand-foot syndrome and diarrhea was lower in capecitabine combination compared to capecitabine monotherapy.. Capecitabine-based combination chemotherapy showed superiority over capecitabine monotherapy in terms of PFS and ORR, with no significant difference in OS. Non-hematological adverse effects such as hand-foot syndrome were fewer with a combination regimen. However, hematological adverse events were fewer with capecitabine monotherapy regimen.

Topics: Anthracyclines; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Diarrhea; Female; Hand-Foot Syndrome; Humans; Middle Aged; Progression-Free Survival; Randomized Controlled Trials as Topic; Survival Rate; Taxoids; Treatment Outcome

Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine.. Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine [825 mg/m2 twice daily (b.i.d.), days 1-14] every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 b.i.d., days 1-14) q3w. The primary end point was progression-free survival (PFS) assessed by an independent review committee. The study had 90% power to detect a 30% improvement in PFS.. Overall, 770 patients were randomised. PFS was significantly longer with VC than with capecitabine alone [hazard ratio, 0.84, 95% confidence interval (CI), 0.71-0.99; log-rank P = 0.043; median 5.6 versus 4.3 months, respectively]. Median overall survival was 13.9 versus 11.7 months with VC versus capecitabine alone, respectively (hazard ratio, 0.98; 95% CI, 0.83-1.15; log-rank P = 0.77). No difference in quality of life was observed between the two treatment arms. The most common adverse events (NCI CTCAE version 3.0) in the combination arm were haematological and gastrointestinal. Grade 4 neutropenia was more frequent with VC (12% versus 1% with capecitabine alone); febrile neutropenia occurred in 2% versus 0.5%, respectively. Hand-foot syndrome was less frequent with VC (grade 3: 4% versus 19% for capecitabine alone). Peripheral neuropathy was uncommon in both arms (grade 3: 1% versus 0.3%).. Vinflunine combined with capecitabine demonstrated a modest improvement in PFS and an acceptable safety profile compared with capecitabine alone in patients with anthracycline- and taxane-pretreated locally recurrent/metastatic BC.. NCT01095003.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Chemotherapy-Induced Febrile Neutropenia; Drug Resistance, Neoplasm; Female; Hand-Foot Syndrome; Humans; Middle Aged; Neoplasm Recurrence, Local; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Progression-Free Survival; Quality of Life; Survival Analysis; Taxoids; Vinblastine

The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial.. EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane. Enrolled patients were randomly assigned (1:1) via a hierarchical, dynamic randomisation scheme and an interactive voice response system to trastuzumab emtansine (3·6 mg/kg intravenously every 3 weeks) or control (capecitabine 1000 mg/m. Between Feb 23, 2009, and Oct 13, 2011, 991 eligible patients were enrolled and randomly assigned to either trastuzumab emtansine (n=495) or capecitabine and lapatinib (control; n=496). In this final descriptive analysis, median overall survival was longer with trastuzumab emtansine than with control (29·9 months [95% CI 26·3-34·1] vs 25·9 months [95% CI 22·7-28·3]; hazard ratio 0·75 [95% CI 0·64-0·88]). 136 (27%) of 496 patients crossed over from control to trastuzumab emtansine after the second interim overall survival analysis (median follow-up duration 24·1 months [IQR 19·5-26·1]). Of those patients originally randomly assigned to trastuzumab emtansine, 254 (51%) of 495 received capecitabine and 241 [49%] of 495 received lapatinib (separately or in combination) after study drug discontinuation. In the safety population (488 patients treated with capecitabine plus lapatinib, 490 patients treated with trastuzumab emtansine), fewer grade 3 or worse adverse events occurred with trastuzumab emtansine (233 [48%] of 490) than with capecitabine plus lapatinib control treatment (291 [60%] of 488). In the control group, the most frequently reported grade 3 or worse adverse events were diarrhoea (103 [21%] of 488 patients) followed by palmar-plantar erythrodysaesthesia syndrome (87 [18%]), and vomiting (24 [5%]). The safety profile of trastuzumab emtansine was similar to that reported previously; the most frequently reported grade 3 or worse adverse events in the trastuzumab emtansine group were thrombocytopenia (70 [14%] of 490), increased aspartate aminotransferase levels (22 [5%]), and anaemia (19 [4%]). Nine patients died from adverse events; five of these deaths were judged to be related to treatment (two in the control group [coronary artery disease and multiorgan failure] and three in the trastuzumab emtansine group [metabolic encephalopathy, neutropenic sepsis, and acute myeloid leukaemia]).. This descriptive analysis of final overall survival in the EMILIA trial shows that trastuzumab emtansine improved overall survival in patients with previously treated HER2-positive metastatic breast cancer even in the presence of crossover treatment. The safety profile was similar to that reported in previous analyses, reaffirming trastuzumab emtansine as an efficacious and tolerable treatment in this patient population.. F Hoffmann-La Roche/Genentech.

Topics: Ado-Trastuzumab Emtansine; Adult; Aged; Aged, 80 and over; Anemia; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aspartate Aminotransferases; Breast Neoplasms; Breast Neoplasms, Male; Bridged-Ring Compounds; Capecitabine; Diarrhea; Disease-Free Survival; Female; Hand-Foot Syndrome; Humans; Lapatinib; Male; Maytansine; Middle Aged; Quinazolines; Receptor, ErbB-2; Response Evaluation Criteria in Solid Tumors; Retreatment; Survival Rate; Taxoids; Thrombocytopenia; Trastuzumab; Vomiting; Young Adult

Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. In this randomized, double-blind, placebo-controlled phase III trial, we assessed first- or second-line capecitabine with sorafenib or placebo in patients with locally advanced/metastatic HER2-negative breast cancer resistant to a taxane and anthracycline and with known estrogen/progesterone receptor status.. Treatment with sorafenib with capecitabine, compared with capecitabine with placebo, did not prolong median PFS (5.5 vs. 5.4 months; hazard ratio [HR], 0.973; 95% confidence interval [CI], 0.779-1.217; P = .811) or overall survival (OS; 18.9 vs. 20.3 months; HR, 1.195; 95% CI, 0.943-1.513; P = .140); or enhance overall response rate (ORR; 13.5% vs. 15.5%; P = .515). Any grade toxicities (sorafenib vs. placebo) included palmar-plantar erythrodysesthesia syndrome (PPES; 79.2% vs. 59.6%), diarrhea (47.3% vs. 37.8%), mucosal inflammation (15.4% vs. 6.7%), and hypertension (26.2% vs. 5.6%). Grade 3/4 toxicities included PPES (15.4% vs. 7.1%), diarrhea (4.2% vs. 6.4%), and vomiting (3.5% vs. 0.7%).. The combination of sorafenib with capecitabine did not improve PFS, OS, or ORR in patients with HER2-negative advanced breast cancer. Rates of Grade 3 toxicities were higher in the sorafenib arm.

Topics: Administration, Oral; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Diarrhea; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Hand-Foot Syndrome; Humans; Hypertension; Kaplan-Meier Estimate; Middle Aged; Niacinamide; Phenylurea Compounds; Placebos; Receptor, ErbB-2; Sorafenib; Taxoids; Treatment Outcome

We conducted a phase II study evaluating safety and efficacy of combination gemcitabine and capecitabine therapy for metastatic breast cancer patients following anthracycline and taxane treatment in Korea.. This was a single-arm, non-randomized phase II study. Patients received 1,000 mg/m(2) gemcitabine intravenously over 30 min on days 1 and 8, and 1,250 mg/m(2) capecitabine orally twice daily on days 1-14 until disease progression or intolerable toxicity occurred. This regimen was repeated every 3 weeks. The primary outcome assessed was overall response rate [ORR, complete response (CR) + partial response (PR) as the best response], and secondary outcomes were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) [maintenance of CR + PR + stable disease (SD) for at least 3 months], drug toxicity, and predictive factors for response to this regimen.. Of 41 patients, the ORR was 39.0% (CR 0%; PR 39.0%), and DCR was 78.0% using this chemotherapy. DCR for 6 and 12 months was 68.3 and 26.8%, respectively. Median PFS was 10.0 months [95% confidence interval (CI) 7.8-12.1], and median OS was 25.1 months (95% CI 18.2-32.1). Prominent toxicities were neutropenia and hand-foot syndrome. Most adverse events were well known, relatively moderate, and reversible. Taxane sensitivity [odds ratio (OR) 0.169; 95% CI 0.034-0.826; P = 0.028] and hepatic metastasis (OR 0.097; 95% CI 0.017-0.559; P = 0.009) were significantly predictive of response to gemcitabine and capecitabine combination.. This study showed reproducible anticancer activity and tolerable toxicity of gemcitabine and capecitabine combination therapy in recurrent or metastatic Korean breast cancer patients previously treated with anthracycline and taxane.

Topics: Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Deoxycytidine; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Screening Assays, Antitumor; Female; Fluorouracil; Gemcitabine; Hand-Foot Syndrome; Humans; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neutropenia; Republic of Korea; Severity of Illness Index; Taxoids; Treatment Outcome

Oral administration of cyclophosphamide (CTX) and capecitabine may have a greater potential for treatment of metastatic breast cancer (MBC) due to anti-angiogenesis resulting from the metronomic dosage and upregulation of thymidine phosphorylase by CTX. The purpose of this phase II study was to evaluate the efficacy and safety profile of an all-oral combination of metronomic CTX plus capecitabine for women with anthracycline- and taxane-pretreated MBC.. In this prospective single-center, open-label, phase II trial, patients with measurable disease received oral metronomic CTX 65 mg/m(2) daily on days 1-14 plus capecitabine 1,000 mg/m(2) twice daily on days 1-14. The treatment was repeated every 3 weeks, and continued until disease progression, unacceptable toxicity or withdrawal of informed consent. The primary endpoint of the study was time to progression (TTP).. A total of 68 patients were enrolled and received 537 cycles of chemotherapy with a median of 8 cycles (range: 1-30 cycles) per patient. Sixty-six patients were evaluated for efficacy with all patients for toxicity. With a median follow-up time of 26 months, the median time to progression was 5.2 months (95% CI, 4.2-6.2 months), and the median overall survival was 16.9 months. The overall response rate was 30.3% (95% CI, 20-43%). Clinical benefit rate was 53.0% (95% CI, 38-62%). The doublet was well tolerable, with anorexia (7.5%), the only grade 3/4 adverse events occurring in more than 5% of patients. Grade 3 hand-foot syndrome was 4.4%.. The all-oral combination of metronomic CTX plus capecitabine is an effective and convenient and well-tolerated regimen for MBC. (ClinicalTrials.gov number, NCT00589901).

Topics: Administration, Oral; Adult; Aged; Anorexia; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Cyclophosphamide; Deoxycytidine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Hand-Foot Syndrome; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Metastasis; Prospective Studies; Taxoids; Treatment Outcome

To evaluate the efficacy and safety of docetaxel plus capecitabine (DC) combination as salvage treatment in anthracycline- and taxane-pretreated patients with metastatic breast cancer (MBC).. Patients with MBC who had disease progression after initial chemotherapy with anthracyclines (n = 29; 100 %) and taxanes (n = 11; 37.9 %) were treated with oral capecitabine 950 mg/m(2) twice daily on days 1-14 and docetaxel 75 mg/m(2) on day 1 every 3 weeks. Nineteen (65.5 %) patients received this regimen as second line and 10 (34.5 %) as ≥3rd line of therapy. All patients were evaluable for response and toxicity.. Complete response occurred in two (6.9 %) patients and partial response in eleven (37.9 %) for an overall response rate of 44.8 % (95 % CI 26.7-62.9 %). Eleven women (37.9 %) had stable disease and five (17.2 %) progressive disease. Of the eleven patients previously treated with anthracyclines and taxanes, five (45.5 %) responded to DC combination. The median duration of response was 5.7 months (range 3.4-64.2), the median time to disease progression 9.3 months (range 1.2-58), and the median overall survival 25.5 months. No toxic death occurred. Neutropenia grade 4 occurred in 58.6 % of patients and three of them (10.3 %) developed neutropenic fever. Non-hematological toxicities were manageable with grade 3 hand-foot syndrome occurring in 6.9 % of the patients, fatigue in 3.4 %, and neurotoxicity in 3.4 %.. The DC combination is a valuable regimen as salvage treatment in anthracycline- or anthracycline and taxane-pretreated patients with MBC.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Deoxycytidine; Disease Progression; Docetaxel; Drug Administration Schedule; Fatigue; Female; Fever; Fluorouracil; Hand-Foot Syndrome; Humans; Middle Aged; Neoplasm Metastasis; Nervous System Diseases; Neutropenia; Remission Induction; Salvage Therapy; Taxoids; Treatment Outcome

To evaluate the efficacy and safety of cisplatin and capecitabine combination (XP) therapy for patients with metastatic triple negative breast cancer (TNBC) progressing after anthracycline and taxane treatment.. Twenty-nine metastatic TNBC patients were prospectively enrolled to receive capecitabine (1, 000 mg/m(2) twice daily on days 1-14) and cisplatin (75 mg/m(2) on day 1) , repeated every 3 weeks.. With a median of 6 cycles of XP, all 29 patients were evaluable for response, including 18 PR (62.1%), 6 SD (20.7%), 5 PD (17.2%) and no CR. The response rate was 62.1%. Patients with earlier stage at diagnosis (stage I to IIIA), longer post-operative disease free survival (>2 years) and less metastatic sites (≤ 3) obtained significantly higher response rate than patients with later stage at diagnosis (stage IIIB to IV), shorter post-operative disease free survival (≤ 2 years) and more metastatic sites (>3). The leading side effects were grade 1/2 gastrointestinal and hematological toxicities. Grade 3/4 toxicities included neutropenia (34.5%), leukocytopenia (31.0%), anemia (6.9%), thrombocytopenia (3.4%), nausea/vomiting (20.7%), stomatitis (3.4%), and hand-foot syndrome (3.4%).. Cisplatin and capecitabine combination therapy is an active and well-tolerated doublet treatment in metastatic TNBC patients progressing after anthracycline and taxane treatments.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Capecitabine; Cisplatin; Disease-Free Survival; Female; Hand-Foot Syndrome; Humans; Leukopenia; Neutropenia; Prospective Studies; Taxoids; Treatment Outcome; Triple Negative Breast Neoplasms