Many lung cancer patients have coexisting ILD, and these patients have a high risk of developing chemotherapy-induced ILD. In addition, patients with DILD who underwent EGFR-TKI therapy and 2 or more prior chemotherapy regimens had a higher risk of fatal outcome.

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Pemetrexed, a chemotherapeutic drug, is highly active in non-small cell lung cancer and malignant pleural mesothelioma. Unfortunately, rashes are more commonly associated with pemetrexed than other chemotherapies, and it is recommended that patients receive corticosteroids (8 mg/d of dexamethasone) for 3 d, including the day of pemetrexed administration (day 1). However, the efficacy of corticosteroids in this context has not been fully verified. In this retrospective study, we evaluated the medical records of 78 patients who received pemetrexed between April 2009 and March 2014, to confirm whether supplementary corticosteroids prevented rash development. The incidence of rash was lower in the 47 patients who received supplementary corticosteroids (after day 1) compared with the incidence among the 31 patients who did not receive supplementary corticosteroids (19.1% vs. 38.7%). The average cutoff dosage of supplementary corticosteroids on day 2 and day 3 was 1.5 mg/d of dexamethasone, as calculated using the receiver operating characteristic curve, and the odds ratio was 0.33 (95% confidence interval: 0.12-0.94). Administration of ≥1.5 mg of corticosteroids on day 2 and day 3 significantly reduced the severity of the rash compared to no supplementary treatment (grades 2/3, 13.3% vs. 33.3%, p<0.05). However, increasing the dose of corticosteroids had no additional effect on rash development. These results suggest that ≥1.5 mg of supplementary dexamethasone on day 2 and day 3 (in addition to day 1) may be necessary for preventing pemetrexed-induced rash, but high doses of dexamethasone (e.g., 8 mg/d) are unnecessary.Key words pemetrexed; rash; dexamethasone; corticosteroid; risk factor Pemetrexed (Alimta, Eli Lilly and Co.) is a novel multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. 1,2) These multiple targets may explain the broad and preferable antitumor activity of pemetrexed, which has been evaluated in non-small cell lung cancer (NSCLC), malignant pleural mesothelioma (MPM), head, neck, cervical, breast, gastric, colorectal, pancreatic, and bladder cancers. [3][4][5][6][7][8][9][10][11][12][13][14] Pemetrexed is currently approved in combination with platinum (cisplatin or carboplatin) as a first-line treatment, and as a single-agent second-line treatment, for MPM and NSCLC. 15,16) Moreover, cisplatin plus pemetrexed provides improved survival and reduced toxicity in patients with non-squamous NSCLC, compared to cisplatin plus gemcitabine. 17) Interestingly, multivariate analysis has revealed that increasing levels of homocysteine and methylmalonic acid are correlated with a toxic increase in pemetrexed. 18) The risks associated with severe pemetrexed toxicity, such as neutropenia, thrombocytopenia, infection, and diarrhea, can be reduced by decreasing homocysteine and methylmalonic acid levels by supplementing patients with folic acid and vitamin B 12 . 18) Unfortunately, rash is one of the most common adverse events that ...

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Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF) for treatment of metastatic colorectal cancer. Recently, much evidence has suggested that bevacizumab-induced hypertension might be predictive of the eŠect of bevacizumab. The aim of our study is to retrospectively assess the relationship between the onset of hypertension and the activity of bevacizumab in Japanese metastatic colorectal cancer patients. Between July 2007 and December 2010, 36 patients (median age 66 years; 36 81 years) with metastatic colorectal cancer were assigned to receive bevacizumab in combination with either mFOLFOX6 (5-FU, levofolinate and oxaliplatin) or FOLFIRI (5-FU, levofolinate and irinotecan) at the Tokushima University Hospital. A patient who had increase by ＞20 mmHg in diastolic blood pressure or had increase to ＞150/100 mmHg or received antihypertensive treatment was deˆned as hypertensive. The objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were compared between the hypertensive group (n＝10) and non-hypertensive group (n＝26). ORR and DCR were 60.0％ and 100％, respectively, in the hypertensive group and ORR and DCR were 23.1％ and 80.8％, respectively, in the nonhypertensive group. These diŠerences were statistically signiˆcant ( p＜0.05). The median PFS tended to be longer in the hypertensive group (65.0 weeks) than in the non-hypertensive group (40.0 weeks). Our data suggested that bevacizumab-induced hypertension may be predictive of the eŠect of bevacizumab in Japanese metastatic colorectal cancer patients.