A Comparative Study of Transdermal Buprenorphine and Oral Morphine in the Treatment of Chronic Pain of Malignant Origin.

BACKGROUND AND OBJECTIVE: The study was designed to compare the efficacy and adverse effects of buprenorphine transdermal (TD) against oral morphine in pain management of cancer patient. METHODS: A randomized open-labeled prospective study was done in palliative cancer pain clinic in a tertiary care medical college between August 2017 and January 2018, to compare the efficacy (pain assessed by VAS) and adverse events (CTCAEv4) between arm A, buprenorphine TD, (20 µg/h, extended 7 days formulation) and arm B, oral morphine (10mg immediate releasing formulation). Patients with solid tumour malignancies with VAS score >40 (moderate to severe pain) were included in study. RESULTS: 63 patients were analyzed. Commonest primary cancers were breast in females and head and neck in male individuals in both arms. Initial VAS score of arm A and arm B were 81.25 and 82.26 respectively. By 1st week, 11 arm A patients were relieved from pain. Another 17 patients of arm A became pain free by 2nd week, total dose of 40 µg/h. Only 4 patients needed 60 µg/h for pain relief. In arm B, 2 patients were relieved by 1 week with total 30mg/day morphine, 11patients were relieved with 60 mg/day by 2nd week and 12 patients with 90 mg/day. 6 patients were relieved with 120 mg/day dose at the end of 4th week. Nausea and constipation were stastically higher in Arm B compared to that of Arm-A. CONCLUSIONS: TD Buprenorphine had similar efficacy with oral morphine, with better toxicity profile and better compliance.

Fixed dose combination of capecitabine and cyclophosphamide in metastatic breast cancer: Results from THE ENCLOSE phase 2/3 randomized multicenter study.

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.

Different fractionation schedules of radiotherapy in locally advanced head and neck malignancy: A prospective randomized study to compare the results of treatment and toxicities of different protocols.

CONTEXT: Altered fractionated radiotherapy may have better result than conventional radiotherapy and concomitant chemoradiotherapy to treat locally advanced head and neck cancers. AIMS: Evaluation of the response and toxicities in different fractionated radiotherapy schedules in locally advanced head and neck cancer. MATERIALS AND METHODS: Sixty four histologically proved patients of locally advanced head and neck cancer were included in the study according to protocol and were randomized into three arms. Arm A (n = 21) received 66 Gy in 33 fractions (5 fractions/week from Monday to Friday) single fraction daily in 6½ weeks along with concomitant chemotherapy (injection Cisplatin 30 mg/m(2) intravenous once weekly) for 6 weeks. Arm B (n = 21) received 66 Gy in 33 fractions (6 fractions per week) single fraction daily in 5½ weeks, and arm C (n = 22) received late hyperfractionation after 3 weeks; 30 Gy in 15 fractions in 3 weeks followed by 1.4 Gy twice daily (time gap between 2 fractions were 6 hours) for 15 days with a total of 72 Gy in 6 weeks. Response to treatment, compliance, and toxicities were compared in all the three arms. STATISTICAL ANALYSIS USED: Frequency table and chi square tests done. RESULTS: Baseline data were comparable in all the three arms. Complete response in arm A, arm B, and arm C were 15%, 26.315%, and 23.81%, respectively (P = 0.339). Grade 1 Neutropenia in arm A was 15%, arm B was 26.32%, and arm C was nil (P = 0.0486). CONCLUSION: Altered fractionation and concurrent chemoradiation showed similar response with comparable acute toxicities except nutropenia, which was significantly higher in arm B.