Circulating amphiregulin and transforming growth factor‐α (TGF‐α) have been found to be correlated with an unfavorable response to gefitinib based on the identification of patients with a higher probability of resistance to the drug. However, the association between an epidermal growth factor receptor (EGFR) somatic mutation and the overexpression of its ligands has not been determined. To verify the clinical significance of the two serum markers and EGFR mutation status, we determined serum amphiregulin and TGF‐α levels by enzyme‐linked immunosorbent assay in 93 patients with advanced non‐squamous, non‐small cell lung cancer and EGFR somatic mutation status using the peptic nucleic acid‐locked nucleic acid clamp method in 46 cases. The relationship between each independent clinicopathological variable and the response to gefitinib therapy was examined. We also evaluated the risk factors associated with prognosis. Fourteen (41.0%) of 34 progressive disease cases were positive for amphiregulin ( P = 0.007). Eleven (32.4%) of 34 progressive disease cases were positive for TGF‐α ( P = 0.005). The median survival time of patients with the EGFR somatic mutation was significantly longer ( P = 0.01). The same was true of amphiregulin‐ ( P = 0.046) and TGF‐α‐negative patients ( P < 0.01). In multivariate analysis, serum TGF‐α positivity (hazard ratio, 2.558; P = 0.005) and the wild type EGFR gene (hazard ratio, 1.894; P = 0.003) were significant independent prognostic factors. Our study demonstrates that the status of the serum EGFR ligand, in addition to EGFR activating mutation, is a predictive factor for response to gefitinib therapy. ( Cancer Sci 2008; 99: 2295–2301)
Introduction: Trifluridine/tipiracil (TAS-102) and Regorafenib (REG) have shown promising activity in patients with heavily pretreated metastatic colorectal cancer (mCRC). The aim of this study was to compare the efficacy and safety of TAS-102 and REG alone in patients with mCRC refractory to standard chemotherapies. Methods: From May 2014 to December 2017, 135 patients with mCRC were treated with TAS-102 or REG as salvage-line therapy. Efficacy, safety and clinical outcomes were retrospectively evaluated. Inclusion criteria were histologically confirmed colorectal adenocarcinoma; refractory or intolerant to fluoropyrimidine, oxaliplatin, irinotecan, anti-VEGF therapy and anti-EGFR antibody (for tumours with wild-type RAS); measurable or evaluable lesion; age ≥ 20 years; Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2; and written informed consent. The clinical outcomes were evaluated using the Cox's proportional hazard models. Results: Among 135 patients, 77 received TAS-102 (median age 77 y, male 49%, ECOG PS 0 62%, RAS wt 43%) and the other 58 received REG (median age 66 y, male 53%, ECOG PS0 64%, RAS wt 51%). With a median follow-up of 5.8 months (range, 1.5 to 19.0), median progression-free survival was statistically longer in the TAS-102 group than in the REG group (TAS-102 2.9 vs REG 2.0 months; HR = 0.591, p = 0.0035). No significant difference in overall survival between TAS-102 and REG (TAS-102 10.4 vs REG 9.2 months; HR = 1.14, p = 0.57) was observed. Conclusion: TAS-102 and REG showed equivalent survival benefit in the treatment of mCRC which had progressed after standard therapies.
We herein report the first case in which an escalated dose of sunitinib was effective, even after dose reduction. A 64-year-old man with gastrointestinal stromal tumor of the small intestine discontinued adjuvant imatinib because of interstitial pneumonia. After two years, peritoneal recurrence was detected. Sunitinib was started at 50 mg/day for 4 weeks every 6 weeks, after which the dosage was reduced to 37.5 mg/day because of grade 1 gastritis, stomatitis, and a fever. Four months later, computed tomography showed progressive disease. As the adverse events were well-controlled by medication, we escalated the dose to 50 mg/day and achieved a partial response.
Background/Aim: In later-line treatment of metastatic colorectal cancer (mCRC), trifluridine/tipiracil is often selected because regorafenib is difficult to use in patients with comorbidities such as thrombosis, hemorrhage, or cardiac events. However, the safety and efficacy of trifluridine/tipiracil in these patients is not clear. Patients and Methods: The clinical outcomes of trifluridine/tipiracil were retrospectively investigated in patients who were ineligible for regorafenib because of comorbidities. Results: Among the 27 patients who received trifluridine/tipiracil, many had comorbidities of deep venous thrombosis or hemorrhage. The median overall survival was 12.4 months, and the median progression-free survival was 2.8 months. The median overall survival was 7.7 months in 19 patients without subsequent regorafenib. Grade 3 or higher toxicities were found in 51% of patients. No treatment discontinuation because of comorbidities was observed. Conclusion: Trifluridine/tipiracil can be safely administered while maintaining efficacy in patients who were ineligible for regorafenib.
Erlotinib plus gemcitabine is one of the standard chemotherapies for unresectable pancreatic cancer. Pancreatic cancer has the highest frequency of KRAS gene mutations among human cancers, and some studies suggest that KRAS status might be a predictive biomarker for anti-epidermal growth factor receptor treatment. However, the reliability of this biomarker has not been confirmed. Here, we evaluated the impact of KRAS mutations in pancreatic cancer patients treated with first line gemcitabine-based chemotherapy. 23 patients treated with gemcitabine-based chemotherapy whose KRAS status could be examined from primary or metastatic lesions were enrolled. KRAS mutations were analyzed by sequencing codons 12 and 13. We retrospectively evaluated the correlation between KRAS status, and prognosis and treatment efficacy. Patient characteristics were as follows: median age 68 years, male/female=6/17, PS 0/1=9/14, TNM stage III/IV=1/22, and gemcitabine alone/erlotinib plus gemcitabine=13/10. Among the 23 patients, KRAS codon 12 was mutated in 15, one of whom also had mutation on codon 13. Median progression-free survival (PFS) and overall survival (OS) of all patients were 4.3 months (95% confidence interval (CI): 3.1 to 5.4) and 8.1 months (95% CI: 5.9 to 10.0; events in 96%), respectively. KRAS status showed no association with PFS (p=0.310), OS (p=0.934), or the efficacy of treatment with (p=0.833) or without erlotinib (p=0.478). Thus, in this study, there was no correlation between KRAS status and the efficacy of first line chemotherapy with gemcitabine with or without erlotinib. Identification of a rationale for personalized medicine in pancreatic cancer will require further exploratory prospective studies.
Abstract Background Reports of hepatitis B virus (HBV) reactivation in solid tumors are very limited, and their frequencies and risk factors were previously unknown. Aim To evaluate the prevalence and risk factors of HBV reactivation in patients with solid tumors with resolved HBV infection. Methods All 1088 patients with solid tumors were assessed for eligibility; 251 patients had resolved HBV infection (negative for HBs antigen and positive for anti‐HBc antibody and/or positive for anti‐HBs antibody), and HBV‐DNA was assessed for 243 of these patients in whom we analyzed the prevalence of HBV reactivation. Risk factors for HBV reactivation were exploratorily evaluated by analysis of a case–control study. Results The prevalence of HBV‐DNA reactivation was 2.1% (95% confidence interval [CI], 0.3–3.9%). We did not observe any exacerbation of HBV‐DNA by early intervention. A low anti‐HBs antibody titer (<10.0 mIU/mL) and high average daily dexamethasone dose (>1.0 mg/day) were high risk factors, with odds ratios of 5.94 (95% CI, 1.15–30.6, P = 0.03) and 8.69 (95% CI, 1.27–58.8, P = 0.02), respectively. Conclusion HBV reactivation in solid tumor patients was relatively rare. Therefore, risk factors that can identify targets for HBV screening must be determined in future studies.
