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ABSTRACT: Metastatic breast cancer (MBC) patients with rapid disease relapse after neo/adjuvant chemotherapy including anthracyclines and taxanes have limited treatment options and their efficacy is marginal. Two phase III studies compared ixabepilone plus capecitabine vs. capecitabine alone as first-line treatment in MBC patients pretreated with anthracyclines and taxanes in the neo/adjuvant setting. Here we report the efficacy and safety of these treatments in a prespecified subset of patients whose disease relapsed within 12 months.
Of 1973 patients across two studies, 293 relapsed within 12 months of neo/adjuvant treatment and received ixabepilone plus capecitabine (n = 149) or capecitabine alone (n = 144) as first-line chemotherapy for MBC. Analysis included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and toxicity.
In 293 patients, ixabepilone plus capecitabine, as compared to capecitabine alone, increased PFS (median: 5.6 months vs. 2.8 months; hazard ratio, 0.58; p < 0.0001), ORR (46% vs. 24%) and OS (median: 15.1 months vs. 12.5 months; hazard ratio, 0.84; p = 0.208). Major toxicities of this regimen included neuropathy, neutropenia and hand-foot syndrome, but were manageable.
Patients with breast cancer with early relapse following neo/adjuvant treatment with anthracyclines and taxanes may benefit from ixabepilone plus capecitabine. (ClinicalTrials.gov identifiers: NCT00080301 and NCT00082433.).
Breast (Edinburgh, Scotland) 09/2011; 21(1):89-94. · 2.09 Impact Factor
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Carlos H Barrios,
David Hernandez-Barajas,
Michael P Brown,
Se-Hoon Lee, Luis Fein,
Jin-Hwang Liu,
Subramanian Hariharan,
Bridget A Martell,
Jinyu Yuan,
Akintunde Bello,
Zhixiao Wang,
Rajiv Mundayat,
Sun-Young Rha
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ABSTRACT: Sunitinib at 50 mg/day on the 4-weeks-on-2-weeks-off schedule is the current approved regimen for advanced/metastatic renal cell carcinoma (mRCC). Escudier et al reported that continuous, once-daily dosing with sunitinib 37.5 mg had a manageable safety profile and significant antitumor activity as second-line mRCC therapy. In this prospective, multicenter, phase II study, we evaluated the activity of continuous once-daily dosing with sunitinib 37.5 mg as first-line mRCC treatment.
One hundred nineteen treatment-naive patients with measurable mRCC received sunitinib. The primary endpoint was objective response; secondary endpoints included progression-free survival (PFS), safety, pharmacokinetic measurements, exploration of response biomarkers, and patient reported outcomes (PRO).
Objective response rate (ORR) was 35.3%; median response duration was 10.4 months; 36% of patients had stable disease ≥12 weeks. Median PFS at 1 year was 9 months, and 1-year survival probability was 67.8%. The most common any-grade treatment-related adverse events (AEs) were diarrhea (50%) and hand-foot syndrome (43%); the most common grade 3-4 treatment-related AEs were hand-foot syndrome (13%), neutropenia (11%), and diarrhea (9%). Steady-state pharmacokinetics were reached within 3 weeks, with no disproportionate accumulation of sunitinib or its active metabolite throughout the study. No significant correlations between trough drug, active metabolite, or soluble protein levels and clinical response were observed. PRO was largely maintained, although fatigue appeared to worsen after treatment started, with improvement over time.
Continuous once-daily dosing with sunitinib 37.5 mg was active with a manageable safety profile as first-line mRCC therapy, making this a feasible alternative dosing regimen.
Cancer 09/2011; 118(5):1252-9. · 4.77 Impact Factor
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ABSTRACT: The aim of this multicenter phase II study was to demonstrate the activity of the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody cetuximab combined with irinotecan in the treatment of Latin American patients with EGFR-expressing metastatic colorectal cancer (mCRC) in whom previous treatment with an irinotecan-containing regimen had failed.
Patients received cetuximab, as a 400 mg/m2 initial infusion followed by 250 mg/m2 weekly, plus the same irinotecan regimen that had previously failed, until the occurrence of disease progression or unacceptable toxicity. The primary endpoint was response. Secondary endpoints included progression-free survival (PFS), duration of response, overall survival (OS), and safety.
Seventy-nine patients received treatment. One patient had a complete response, 20 had partial responses, and disease was stabilized in 23 patients, giving an overall response rate of 27% and a disease control rate of 56%. The median duration of response was 23.9 weeks. Median PFS was 17.4 weeks, median OS was 9.2 months, and the 12-month OS rate was 38%. The most common adverse events according to System Organ Class were skin and subcutaneous tissue disorders (91% of the patients). Grade 3/4 adverse events occurred in 45 patients (57%), with the most common being diarrhea (20%), neutropenia (11%), and rash (6%). Seven patients (9%) had grade 3/4 acne-like skin rash. No grade 3/4 infusion-related reactions were reported.
Cetuximab in combination with irinotecan is active and tolerable in Latin American patients with mCRC progressing on irinotecan, with a safety profile similar to that described in European studies.
Clinical Colorectal Cancer 12/2010; 9(5):282-9. · 1.68 Impact Factor
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Stephen Chia,
William Gradishar,
Louis Mauriac,
Jose Bines,
Frederic Amant,
Miriam Federico, Luis Fein,
Gilles Romieu,
Aman Buzdar,
John F R Robertson,
Adam Brufsky,
Kurt Possinger,
Pamela Rennie,
Francisco Sapunar,
Elizabeth Lowe,
Martine Piccart
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ABSTRACT: The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor-positive (HR+) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure.
Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR+ advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily.
A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane (n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups (hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate (7.4% v 6.7%; P = .736) and clinical benefit rate (32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant.
Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.
Journal of Clinical Oncology 05/2008; 26(10):1664-70. · 18.37 Impact Factor
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ABSTRACT: Previous studies have indicated that, in combination with cisplatin, fixed dose rate gemcitabine may be more efficacious than standard infusion gemcitabine. This open-label, randomised phase II study was aimed to compare the efficacy and safety of these regimens as treatment for advanced non-small cell lung cancer (NSCLC) in Latin American patients. Sixty-four patients were randomised to receive up to six cycles of treatment with cisplatin 75 mg/m(2) on Day 1 plus either gemcitabine 1000 mg/m(2) over 30 min on Days 1 and 8 of a 21-day cycle (standard arm, N=33) or gemcitabine 1000 mg/m(2) at a fixed dose rate of 10 mg/m(2)/min on Days 1 and 8 of a 21-day cycle (FDR arm, N=31). In the standard arm, 9 of 33 (27%) patients responded compared with 6 of 30 (20%) patients in the FDR arm (odds ratio: 0.67, 95% CI, 0.21-2.2; p=0.56). Median overall survival was 7.5 months in the standard arm and 9.9 months in the FDR arm. One-year survival rates were 35% and 37% in the standard arm and the FDR arm, respectively. Patients in the FDR arm experienced more grade 3/4 haematological toxicity than those in the standard arm (48% versus 21%). The results of this trial do not support FDR administration of gemcitabine in preference to the standard administration in Latin American patients with NSCLC.
Lung Cancer 11/2007; 58(1):80-7. · 3.43 Impact Factor
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ABSTRACT: It has been stated that simple cholecystectomy is sufficient treatment for all patients with pT1 gallbladder cancer. However, other authors note the necessity of carrying out extended surgery when there is muscular-layer involvement.
A consecutive series of gallbladder carcinomas with lamina propria or muscular layer invasion were analyzed. Between July 1982 and December 2000, 51 patients with pT1 gallbladder carcinomas were treated with simple cholecystectomy (group A, 25 patients with lamina propria-invasion; group B, 26 patients with muscular-layer invasion). Patients with intraepithelial carcinomas were excluded from the study.
There were no differences between the groups in average age, sex ratios, association with other tumors, histologic type, malignancy grade, cholecystitis type, macroscopic aspects, lymph node status, or treatment applied. After an average of 6 years' follow-up, no patients in group A and nine patients (34.6%) in group B died due to gallbladder carcinoma. Cystic lymph nodes could be studied in five of these nine patients who relapsed, and the results were negative for metastasis. Lymphatic or venous invasion was observed in five of these nine patients.
According to these results, cholecystectomy is not sufficient treatment for gallbladder carcinoma with muscular-layer invasion.
Journal of Hepato-Biliary-Pancreatic Surgery 02/2006; 13(6):562-6. · 1.60 Impact Factor
