ABSTRACT
AIM: To evaluate pharmacokinetics, efficacy and safety of fixed-dose combination (FDC) of oral capecitabine + cyclophosphamide in metastatic breast cancer (MBC) patients progressing after anthracycline and/or taxane chemotherapy. METHODS: In this prospective, adaptive, phase-2/3, open-label study (CTRI/2014/12/005234), patients were randomized (1:1:1) to three FDC doses (doses/day: D1, capecitabine + cyclophosphamide 1400 mg + 60 mg; D2, 1800 mg + 80 mg; D3, 2200 mg + 100 mg) for 14 days, in 21-day cycles. In Part-I, multiple-dose pharmacokinetics and optimal dose(s) were evaluated with futility analysis. Group(s) with <3 responders based on best overall response rate (BOR, complete response [CR]+partial response [PR]), were discontinued. Efficacy (BOR, disease control rates [DCR; CR + PR + stable disease]) and safety of optimal dose(s) were evaluated in Part-II. RESULTS: Of 66 patients (n = 22/group) in Part-I, pharmacokinetics (D1 = 7/22, D2 = 9/22, D3 = 8/22) showed dose-proportionality for cyclophosphamide and greater than dose-proportionality for capecitabine. Modified intent-to-treat (mITT) analysis showed BOR of 7.14% (1/14) in D1 (discontinued), and 22.22% (4/18) each in D2 and D3, respectively. In Part-II, 50 additional patients were randomized in D2 and D3 (n = 144; total 72 [22 + 50] patients/group). mITT analysis in D2 (n = 54) and D3 (n = 58) showed BOR of 29.63% (16/54, 95%CI: 17.45-41.81%) and 22.41% (13/58, 95%CI: 11.68-33.15%), respectively. DCR in D2 and D3 were 87.04% (47/54, 95%CI: 78.08-96.00%) and 82.76% (48/58; 95%CI: 73.04-92.48%) after 3 and 57.41% (31/54; 95%CI: 52.41-79.50%) and 50.00% (29/58; 95%CI: 40.40-67.00%), after 6-cycles, respectively. Hand-foot syndrome (16.67%), vomiting (9.72%) in D2, and hand-foot syndrome (18.06%), asthenia (15.28%) in D3 were most-common adverse events. CONCLUSION: FDC of capecitabine + cyclophosphamide (1800 + 80 mg/day) showed high disease control rates and good safety profile in MBC patients.
Subject(s)
Breast Neoplasms , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Capecitabine/therapeutic use , Cyclophosphamide/adverse effects , Deoxycytidine/adverse effects , Female , Fluorouracil/therapeutic use , Humans , Neoplasm Metastasis , Prospective Studies , Treatment OutcomeABSTRACT
Non-occlusive mesenteric ischemia (NOMI) is a disorder with an extremely high mortality. Salvage of affected patients requires early recognition and aggressive intervention to prevent intestinal gangrene. We present a case of NOMI developing after esophagectomy and discuss the pathophysiology diagnosis and therapy.
Subject(s)
Esophagectomy/adverse effects , Ischemia/etiology , Mesenteric Vascular Occlusion/etiology , Mesenteric Vascular Occlusion/pathology , Postoperative Complications/pathology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/surgery , Fatal Outcome , Humans , Ischemia/pathology , Ischemia/physiopathology , Male , Mesenteric Arteries/pathology , Mesenteric Arteries/physiopathology , Mesenteric Vascular Occlusion/physiopathology , Mesenteric Veins/pathology , Mesenteric Veins/physiopathology , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/drug therapy , Nitrates/therapeutic use , Postoperative Complications/physiopathology , Vasodilator Agents/therapeutic useABSTRACT
Laparoscopic approach to rectal cancer is technically challenging even for experienced laparoscopic surgeons. Therefore, in a locally recurrent rectal cancer not many surgeons would be keen to adopt the relaparoscopy approach. In this video article, we present a case of salvage laparoscopic abdominoperineal resection performed for an isolated anastomotic recurrence developed 13 months after a laparoscopic ultralow anterior resection.
