Use of Leflunomide for Treatment of Cytomegalovirus Infection in Recipients of Allogeneic Stem Cell Transplant.

Cytomegalovirus (CMV) reactivations are common after allogeneic stem cell transplants, and pre-emptive therapy has been found to be effective. However, in India, treatment options are limited because of high cost and toxicity of ganciclovir and unavailability of cidofovir and foscarnet. Leflunomide is a cheap and easily available anti-rheumatoid arthritis drug that has been shown to have anti-CMV properties both in vitro and in vivo. It also has been used effectively for CMV reactivation after renal transplants. In this retrospective analysis, we analyzed 70 allogeneic stem cell transplants that were conducted between April 2015 and February 2017. There were 49 episodes of CMV reactivations in 43 patients in this period. Leflunomide was used in 24 episodes. It was effective in CMV clearance in 9 of the 24 episodes (38%). When the CMV copy number was <2 × 103 copies/mL, leflunomide was effective in 9 of 17 (53%) episodes, but when the copy number was >2 × 103, leflunomide was ineffective in all of the 7 episodes. This difference was statistically significant (P= .022 by Fisher exact test), suggesting that leflunomide may be more effective in clearance of CMV when copy numbers are low.

Modified 5-fluorouracil/leucovorin/irinotecan as a feasible and efficacious second-line chemotherapeutic regimen in advanced gastric cancers.

BACKGROUND: Modified 5-fluorouracil/leucovorin/irinotecan (mFOLFIRI) is a commonly used combination second-line chemotherapeutic regimen in advanced gastric cancer (AGC). MATERIALS AND METHODS: Patients diagnosed with AGC, receiving biweekly mFOLFIRI between July 2013 and June 2016, as second-line chemotherapy were retrospectively analyzed for tolerance, prognostic factors, event-free survival (EFS), and overall survival (OS). RESULTS: Overall, 91 patients were administered a median of 6 cycles of therapy. Response rate was 29.7% and clinical benefit rate was 57.2%. With a median follow-up of 11.5 months, median EFS was 3.98 months (95% confidence interval [CI]: 2.54-5.41) and median OS was 7.73 months (95% CI: 5.30-10.15). Common Grade 3 and Grade 4 adverse events were neutropenia (18.7%), febrile neutropenia (9.9%), thrombocytopenia (7.7%), and vomiting (4.4%). Nearly 33% of patients required dose modification during therapy. CONCLUSIONS: mFOLFIRI regimen as a second-line therapy in AGCs appears feasible and efficacious in clinical practice.

Outcome of neoadjuvant chemotherapy in "locally advanced/borderline resectable" gallbladder cancer: the need to define indications.

BACKGROUND: Studies evaluating neo-adjuvant chemotherapy (NACT) exclusively in gallbladder cancer (GBC) are few and there are no randomized trials on the subject. Locally advanced GBC and indications for NACT in GBC are not yet clearly defined. METHODS: We analysed 160 consecutive GBC patients who received NACT based on clinico-radiologic criteria suggesting high-risk disease (TMH Criteria) from January 2010 to February 2016. RESULTS: On initial assessment, 140 (87.5%) patients had T3/T4 disease and 105 (65%) patients were node positive. Response rate and clinical benefit rate was 52.5% and 70% respectively. Sixty six (41.2%) patients could undergo curative intent resection. With a median follow-up of 33 months, the median OS and EFS of the entire cohort were 13 and 8 months respectively. Patient undergoing curative surgery had a statistically superior OS (49 vs. 7 months; p = 0.0001) and EFS (25 months vs. 5 months; p = 0.0001) compared to those who did not. CONCLUSION: Locally advanced GBC remains a disease with poor prognosis. Chemotherapy with neoadjuvant intent in locally advanced/borderline resectable GBC showed good response rates. This resulted in curative surgical resection or disease stabilisation in significant proportion of patients. Patients who undergo definitive surgery after favourable response to NACT experience good survival.

Toxicity and early outcomes of regorafenib in multiply pre-treated metastatic colorectal adenocarcinoma-experience from a tertiary cancer centre in India.

BACKGROUND: Regorafenib is a multikinase inhibitor (MKI) approved for use in multiply pre-treated metastatic colorectal cancers (mCRC). To the best of our knowledge, this is the first report of regorafenib from India. MATERIALS AND METHODS: Records of 23 cases treated with regorafenib at our centre between June 2013 till September 2015 were reviewed. All had received at least two non cross resistant lines of therapy prior to regorafenib. Toxicity was recorded using CTCAE version 4.03. Responses were assessed using RECIST 1.1 criteria. Response evaluation was done every three months or earlier if clinically indicated. Five patients were still on therapy at the time of this report. RESULTS: The median age was 50 years. Thirty-nine percent (9/23) had upfront metastatic disease. Twenty-six percent (6/23) and 39% (9/23) patients had received prior treatment with cetuximab and bevacizumab respectively. Mean duration of regorafenib treatment was 3.8 months. At least one grade III/IV toxicity was noted in 65% (15/23) cases. The most common were handfoot syndrome (HFS) and fatigue seen in 86.9% (20/23) patients. Grade II and III HFS was seen in 65% patients. One patient required stoppage of treatment due to grade III hepatotoxicity. Dose reduction was required for 86.9% (20/23) patients. Best response noted was stable disease in 34.8% (8/23), partial response in 8.7% (2/23) patients and progression in 56.5% (13/23). Median progression free survival was 3 months and median follow-up was 4.5 months. CONCLUSIONS: Regorafenib, although an effective treatment strategy in multiply pre-treated mCRC, is associated with significant side effects.