Vhf Lee

Randomized phase II study of two intercalated combinations of eribulin mesylate and erlotinib in patients with previously treated advanced non-small-cell lung cancer

BACKGROUND This phase II, open-label study investigated intercalated combinations of eribulin and erlotinib in unselected patients with advanced non-small-cell lung cancer previously treated with platinum-based chemotherapies. PATIENTS AND METHODS Eligible patients were randomized to eribulin mesylate 2.0 mg/m(2) on day 1 with erlotinib 150 mg on days 2-16 (21-day regimen) or eribulin mesylate 1.4 mg/m(2) on days 1 and 8 with erlotinib 150 mg on days 15-28 (28-day regimen). The primary end point was objective response rate (ORR). RESULTS One hundred and twenty-three patients received ≥ 1 cycle of therapy (63, 21-day regimen; 60, 28-day regimen). ORRs were 13% [95% confidence interval (CI) 6%-24%] and 17% (95% CI 8%-29%), and disease control rates were 48% (95% CI 35%-61%) and 63% (95% CI 50%-75%) for the 21- and 28-day regimens, respectively. The median progression-free survival and overall survival were similar with both regimens. Both regimens were well tolerated with common grade ≥ 3 toxicities being neutropenia, asthenia/fatigue, and dyspnoea. Sequential administration of erlotinib did not interfere with the pharmacokinetic profile of eribulin. CONCLUSION Intercalated combination of eribulin and erlotinib demonstrated modest activity and the addition of erlotinib did not appear to improve treatment outcome in an unselected population. The 28-day regimen is suitable for further investigation. Clinicaltrials.gov identifier: NCT01104155.

Gefitinib-induced toxic epidermal necrolysis in a patient with metastatic non-small cell lung cancer

Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous condition that is usually caused by a reaction to drugs (80-95%). It is characterised by widespread sloughing of the skin and mucosa. Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is a standard first-line treatment for EGFR-mutated metastatic non–small cell lung cancer. We report a case of TEN complicating gefitinib treatment in a 65-year-old woman with metastatic pulmonary adenocarcinoma. She developed skin eruptions on day 5 of treatment that rapidly evolved to TEN on day 8. This case report highlights the rapidly evolving course of gefitinib-induced TEN and the importance of early diagnosis, prompt withdrawal of the drug, and intensive care.

Impact of CAPOX or FOLFOX4 on Spleen size, Platelet Count and Liver Function when Partnered Cetuximab as First-line Treatment for KRAS Wild-type Metastatic Colorectal Cancer

Objectives: Oxaliplatin can cause hepatic sinusoidal injury and splenomegaly. It remains unknown if the magnitude of injury would differ when oxaliplatin is combined with capecitabine or 5-FU with/without cetuximab. We investigated the impact of 1 st line CAPOX or FOLFOX4 and the additional cetuximab on spleen size, platelet count and liver function in patients with KRAS wild-type metastatic colorectal cancer (mCRC). Methods: 101 Patients planned to receive either CAPOX or FOLFOX4 with/without cetuximab as first-line treatment were prospectively recruited. Changes in spleen size by volumetric measurement after treatment were determined. Correlation studies were performed for factors associated with changes in spleen size, thrombocytopenia and impaired liver function. Results: The spleen enlarged (median +17.9%, P < 0.001) after treatment. Multivariable analysis revealed that capecitabine, its dose intensity and cumulative dose (per 10000mg increase) correlated with splenomegaly (P = 0.01, P = 0.02 and P = 0.006, respectively). Increase in spleen size (P = 0.004) and splenomegaly (P = 0.002) correlated with thrombocytopenia. Dose intensity and cumulative dose of capecitabine (per 10000mg increase) and increase in spleen size correlated with grade 1 impaired liver function (P = 0.01, P = 0.003 and P = 0.04, respectively). Use of cetuximab correlated with less splenic enlargement (+13.7% vs. +22.7%; P = 0.04), especially when coupled with FOLFOX4 rather than CAPOX (+1.1% vs. + 23.0%; P = 0.003). Conclusions: Capecitabine was associated with more splenomegaly which in turn correlated with thrombocytopenia and impaired liver function. Cetuximab offered some protection from further splenic enlargement especially when combined with FOLFOX4.

595PTHE IMPACT OF COMPLETE METABOLIC RESPONSE IN THE TREATMENT OF METASTATIC COLORECTAL CANCER

ABSTRACT Aim: Molecular imaging with 18F-FDG PET scan is increasingly used for monitoring of treatment response in metastatic colorectal cancer. While there is no widely accepted standard for defining partial response, metabolic complete response (mCR) appears as a more reproducible endpoint. We performed a retrospective study to evaluate the impact of mCR on both treatment outcomes and treatment plan. Methods: Patients who were referred to our department for further management of colorectal cancer from Jan 2008 to Dec 2011 were retrospectively reviewed. They were included for subsequent analysis if [1] achieved mCR on 18F-FDG PET scan during first-line therapy, [2] serial PET scans (>= 2) available for demonstration of change in 18F-FDG avidity. The primary endpoint was progression-free survival (PFS). Secondary endpoint were overall survival (OS), time-to-mCR (TTm) and impact of mCR on subsequent treatment plan. Results: Among the 1007 patients referred to us, 356 patients (35%) received systemic therapy for metastatic disease and 202 of them (20%) had PET scan done during the course of systemic therapy. Forty-three patients achieved mCR and 37 of them fulfilled all the criteria for subsequent analysis. mCR was achieved after a median of 4 cycles of systemic therapy (Range 3-12 cycles) after a median TTm of 14weeks (95% CI 12.5-15.5). Subsequent treatment was not altered in 21 patients (56.7%) who had planned drug holiday after six months of therapy. Six and ten of the remaining patients received maintenance therapy and consolidation treatment (resection or radiotherapy), respectively. After a median follow up time of 33 months, the median PFS and OS was 14.4 months (95% CI 10.3 to 18.6) and 47.1 months (95% CI 36.8 to 57.4), respectively. Normal initial CEA ( Conclusions: Favorable outcomes were observed in patients who achieved mCR on 18F-FDG PET scan. Its current impact on treatment decision remains elusive and further studies warranted. Disclosure: All authors have declared no conflicts of interest.