This study retrospectively investigated the clinical features and risk factors of allergic reactions induced by oxaliplatin administration. This study investigated the incidence of allergic reactions and analysed the background and laboratory data in patients with colorectal cancer treated with oxaliplatin-based chemotherapy at Kyushu Medical Center between April 2012 and September 2012. A total of 62 patients were included in this study. The number of patients in the allergic and non-allergic groups was 7 and 55 respectively. The incidence of allergic reactions was 11.3%. We compared the patients' characteristics and laboratory data between the two groups and found that the average dose of dexamethasone in the allergic group was significantly lower than that observed in the non-allergic group (P = 0.0111). Furthermore, the incidence of allergic reactions in the group that received prophylaxis of less than 12 mg of dexamethasone was significantly higher than that observed in the group that received more than 12 mg of dexamethasone (P = 0.0103). In conclusion, a lower dexamethasone dose is a possible risk factor for allergic reactions induced by the administration of oxaliplatin; however, given the retrospective design used in this study, further validation of this finding is warranted.
Irinotecan is a camptothecin analogue with high antitumor efficacy by inhibiting topoisomerase I. This drug was approved for the treatment of a wide variety of solid tumors such as colorectal cancer, and has been widely used in Japan. Especially, combination therapy of irinotecan, 5-fluorouracil and leucovorin (FOLFIRI) has been proven to be highly effective for the treatment of metastatic colorectal cancer. 1,2)The FOLFIRI has become a key regimen in the treatment of metastatic colorectal cancer as a standard option of chemotherapy in many countries including the United States, European countries and also Japan.Irinotecan is a prodrug that is metabolized by carboxylesterase 2 to generate its active metabolite SN-38, which exerts antitumor effects and causes adverse drug reactions (Fig. 1). SN-38 thus formed is further glucuronidated by a hepatic UDP-glucuronosyltransferase 1A1 (UGT1A1), to yield a polar inactive SN-38 glucuronide (SN-38G).3)There are various genetic variants in the UGT1A1 gene that influence the expression or function of encoded protein. UGT1A1*28 is an allele with (TA) 7 TAA within the promoter of the UGT1A1 gene that has been known to be associated with reduced glucuronidation capacity of SN-38 as well as with irinotecan-related dose-limiting toxicities, including severe myelosuppression and delayed-type diarrhea. 4-6)UGT1A1*6 is an allele including a single nucleotide polymorphism (211GϾA) causing an amino acid change (G71R) that relates to reduced catalytic activity. This polymorphism allele is seen in Asian populations including Japanese with a high frequency (0.15 to 0.25), but not in whites.7-9) The UGT1A1*6 has been increasingly clarified to be associated with reduced SN-38 glucuronidation and irinotecan-induced severe toxicity in Asian populations. [8][9][10] Irinotecan, SN-38 and SN-38G are known to be excreted into bile by members of the ATP-binding cassette transporters. ATP-binding cassette, sub-family C, number 2 (ABCC2) is a transporter which is expressed at the apical
Abstract. There is currently no standard method for the detection of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status in colorectal tumors. In the present study, we compared the KRAS mutation detection ability of four methods: direct sequencing, Scorpion-ARMS assaying, pyrosequencing and multi-analyte profiling (Luminex xMAP). We evaluated 73 cases of metastatic colorectal cancer (mCRC) resistant to irinotecan, oxaliplatin and fluoropyrimidine that were enrolled in an all-case study of cetuximab. The KRAS mutation detection capacity of the four analytical methods was compared using DNA samples extracted from tumor tissue, and the detection success rate and concordance of the detection results were evaluated. KRAS mutations were detected by direct sequencing, Scorpion-ARMS assays, pyrosequencing and Luminex xMAP at success rates of 93.2%, 97.3%, 95.9% and 94.5%, respectively. The concordance rates of the detection results by Scorpion-ARMS, pyrosequencing and Luminex xMAP with those of direct sequencing were 0.897, 0.923 and 0.900 (κ statistics), respectively. The direct sequencing method could not determine KRAS mutation status in five DNA samples. Of these, Scorpion-ARMS, pyrosequencing and Luminex xMAP successfully detected three, two and one KRAS mutation statuses, respectively. Three cases demonstrated inconsistent results, whereby Luminex xMAP detected mutated KRAS in two samples while wild-type KRAS was detected by the other methods. In the remaining case, direct sequencing detected wild-type KRAS, which was identified as mutated KRAS by the other methods. In conclusion, we confirmed that Scorpion-ARMS, pyrosequencing and Luminex xMAP were equally reliable in detecting KRAS mutation status in mCRC. However, in rare cases, the KRAS status was differentially diagnosed using these methods. IntroductionCetuximab is a monoclonal antibody that targets the extracellular domain of the epidermal growth factor receptor (EGFR), and is an essential treatment option in patients with metastatic colorectal cancer (mCRC). Numerous researchers have reported that anti-EGFR agents have extremely poor antitumor effects in chemotherapy for mCRC with mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) (1-5), providing clear evidence that administration of anti-EGFR agents is recommended only for mCRC with wild-type KRAS. However, although a number of methods may be used for KRAS mutation testing with varying sensitivity and specificity levels, no standard method has yet been recommended for clinical practice. Therefore, the use of these detection assays is somewhat erratic worldwide.In Japan, cetuximab was administered for ~18 months following its launch in September 2009 without determination of KRAS mutation status, since the above-mentioned analytical methods were not covered by health insurance. The direct sequencing method (6) was covered in April 2010, followed by multi-analyte profiling (Luminex xMAP) technology (7) in March 2011 and Scorpion-ARMS assays (8)
S-1 plus cisplatin is the standard chemotherapy for recurrent gastric cancer. While depression and delirium are frequent in cancer patients, hypomania during chemotherapy is rare. We describe a rare case of hypomania during S-1 plus cisplatin treatment for recurrent gastric cancer. A 66-year-old woman, with no previous psychiatric disorder, received S-1 plus cisplatin for recurrent gastric cancer. She showed peculiar behavior. Physical examination, urine, blood and imaging findings were normal. There was no gastric cancer progression. During psychiatric consultation, she behaved inappropriately. However, she behaved normally while performing daily activities. She manifested a persistently elevated, expansive or irritable mood, clearly different from her usual non-depressed state, meeting hypomania diagnostic criteria. Her condition did not require chemotherapy discontinuation or additional medication. During the second and subsequent S-1 plus cisplatin cycles, symptoms were stable. Cancer patients often have adjustment disorders, depression and delirium, but rarely hypomania. Our patient showed no significant changes in blood biochemistry and brain and whole body imaging. While S-1 plus cisplatin-induced hypomania cannot be excluded, hypomanic symptoms did not improve during the chemotherapy rest period, nor was there deterioration during subsequent cycles, suggesting drug-induced mania to be unlikely. Possible onset mechanisms include manic defense phenomena, common with stressful life events. There are no reports of recurrent gastric cancer patients experiencing hypomania during S-1 or S-1 plus cisplatin therapy, i.e. our patient represents a rare course. Clinicians should recognize psychosis or mood disorders during gastric cancer treatment. Further accumulation of such rare cases might elucidate pathological mechanisms underlying hypomania in cancer patients.
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