Patients with SCLC (Small cell lung cancer) have been treated differently from those with NSCLC (New-small cell lung cancer) as a different disease. Recently, even patients with NSCLC are treated differently according to histological subtypes. This change is associated with the development of new drugs, particularly molecular-targeted drugs. Because Bevacizumab can cause serious adverse effects, patients with squamous cell carcinoma histology and a history of hemoptysis are contraindicated for this drug. Pemetrexed has been approved with an anti-mesothelioma drug and was confirmed to be effective for NSCLC. However, its efficacy was not equally proved among the histological subtypes; only adenocarcinoma patients showed shorter progression-free and prolonged survival periods. Regarding tyrosine kinase inhibitors, the targeted gene alterations occur specifically in adenocarcinoma. Based on these findings, the current therapeutic strategy for NSCLC is based on the histological subtype and mutational status of EGFR and ALK. In this article, transition of the therapeutic strategy for NSCLC, characteristics of targeted gene alterations and efficacies of the targeted therapy are reviewed.

We retrospectively examined the feasibility and outcome of S-1 adjuvant chemotherapy for 18 patients with gastric cancer treated based on the liaison-clinical pathway (liaison group), and compared them with those of 26 patients treated before the induction of the liaison-clinical pathway (non-liaison group). The persistent rate of S-1 adjuvant chemotherapy for one year except for recurrence, the relative performance (RP) value of cases who had received S-1 for one year, and Grade 3/4 adverse events in non-liaison group/liaison group, were 88.5/87.5% (p = 0.93), 87.0/92.9% (p = 0.56), and 26.9/5.6% (p = 0.07), respectively. This did not show a significant difference. The rate of patients administered medication for coexistent diseases in our hospital in the non-liaison group/liaison group was 53.8/0% (p = 0.0002), which reflected the accomplishment of the transfer of medical care for coexistent disease from a hospital to a clinic on the liaison-clinical pathway. Furthermore, a neighboring clinic could be arranged to accommodate 9 (64.3%) of 14 patients living quite far from the hospital in the liaison group. In conclusion, S-1 adjuvant chemotherapy for patients with gastric cancer treated based on the liaison-clinical pathway was feasible, led to the effective practice of sharing between hospital and clinic, and the shorter trip for treatment at a neighboring clinic by patients living far from a hospital.

The current status of treatment with sorafenib, and factors affecting the duration of treatment in patients started on sorafenib for hepatocellular carcinoma from July 2009 until April 2011 in the Department of Gastroenterology at Kobe City Medical Center General Hospital, were examined. Of 21 patients, 12 were able to continue the administration of sorafenib for more than one month, but 9 had to be discontinued within one month due to disease progression, worsening of general condition, and severe adverse reactions. In the group that was discontinued early, the rate of discontinuation due to side effects such as general fatigue, diarrhea, and hepatic encephalopathy was higher than in the long-term treatment group. On the other hand, hand-foot syndrome developed only in one case in both groups. The median value of PIVKA- II at the start of treatment in the long-term and early discontinued treatment groups were 672.5 and 14, 203 mAU/mL, respectively, and the values in the long-term group were significantly lower than those in the early-discontinued group (p < 0.05). From these results, the values of PIVKA-II at the start of sorafenib were considered to be factors affecting the continuation of sorafenib treatment. In addition, the dosing period was considered to be extended to focus on measures to take against the side effects of sorafenib within the early phase. Therefore, it was considered that these factors improved the effect of treatment with sorafenib in patients with hepatocellular carcinoma.

A 78-year-old woman was diagnosed with multiple myeloma (MM: IgG κ type, stage IIIA, ISS III) at a nearby hospital in August 2010. High-dose dexamethasone therapy was ineffective, and she was treated with 2 courses of bortezomib. She was referred to our hospital with back pain and dyspnea in November. She was diagnosed with interstitial pneumonia (IP) and improved rapidly with steroid pulse therapy. Because the involvement of bortezomib was suspected in IP, lenalidomide therapy was selected for MM. Lenalidomide (15 mg) was administered for 2 courses. The patient achieved a PR and the treatment is still ongoing with a good response. According to the interim report on PMS (post-marketing surveillance), 3 of the 1,177 patients treated with lenalidomide developed IP. The dose level was 25 mg in 2 cases and 10 mg in 1 case. The outcomes of these patients were death in 1 case, not recovered in 1 case, and unknown in 1 case. When lenalidomide is used to treat bortezomib-induced IP, there are no rules or regulations about its dose level. In the present case, the dose of lenalidomide (15 mg) was based on the retreatment dose after bone marrow suppression. Low-dose lenalidomide therapy was effective and safe against MM with a bortezomib-associated lung disorder.

A 60-year-old man was examined at a local clinic for difficulty in urinating, and was diagnosed with prostatic hypertrophy. He was referred to our department because his prostate-specific antigen (PSA) level was elevated (276 ng/ml). His Gleason score was 4＋3, there was one bone metastasis in the left ileac bone, and multiple lung metastases were present. The patient was accordingly diagnosed with stage D2 prostate cancer. Lutenizing hormone-releasing hormone (LH-RH) analogue treatment was initiated in April 1999, and 9 months later the PSA level had decreased to 4.3 ng/ml. Six years and 9 months after the start of hormone therapy, the cancer had developed into castration-resistant prostate cancer and the PSA level had risen to 43.8 ng/ml. Paclitaxel-carboplatin therapy was therefore initiated. Eight months after the start of chemotherapy, the PSA level had decreased to 25.9 ng/ml, but 6 years and 1 month later it had risen to 925 ng/ml, and the chemotherapy was discontinued. Docetaxel-predonine therapy was initiated in March 2012. Three months after the start of chemotherapy, the PSA level had decreased to 3.1 ng/ml, and the bone metastasis was reduced.

A 38-year-old man was given a diagnosis of as sigmoid colon cancer and underwent sigmoid colectomy. Post-operative pathological staging was stage IIIb. He then underwent adjuvant chemotherapy. One year and 4 months after the surgery, CT scans revealed multiple liver and lung metastases. He was given mFOLFOX6+bevacizumab, which was changed later to FOLFIRI+bevacizumab. After these chemotherapies, he was admitted to the hospital due to sudden abdominal pain and high grade fever. Obstructive jaundice was initially diagnosed, but detailed study of initial CT revealed intragastric wall abscess. After the drainage of the abscess, his conditions improved. We speculated that the abscess formation was caused by mucosal damage due to bevacizumab.

A 67-year-old man was diagnosed to have sigmoid colon cancer with peritonitis carcinomatosa. The cancer was surgically resected, and he thereafter underwent chemotherapy with mFOLFOX6+bevacizumab. He complained of gingival swelling throughout treatment and osteonecrosis of the jaw was noted. The bevacizumab therapy was therefore discontinued and the necrotic tissue removed. No recurrent necrosis has occurred. The addition of bevacizumab to the FOLFOX or FOLFIRI chemotherapy regimens has been shown to improve the survival rate and response rate in colorectal cancer. Osteonecrosis of the jaw is a rare toxicity of bevacizumab. Bevacizumab might compromise the microvessel integrity in the jaw, which thus may lead to bone necrosis. Osteonecrosis of the jaw in this case recovered after the discontinuation of bevacizumab and the removal of the necrotic tissue. The pathogenesis and treatment of osteonecrosis have not been elucidated.

A woman in her seventies with multiple early stage (0-IIa) gastric cancers was undergoing imatinib therapy for gastrointestinal stromal tumor. Subsequently, she underwent 2-stage endoscopic submucosal dissection (ESD) for these cancers. Both procedures were successful, but she developed exfoliative esophagitis as a complication after the first ESD. To prevent this complication after the second ESD, we used a longer imatinib withdrawal period before the procedure and used general anesthesia during ESD. Although the patient developed exfoliative esophagitis after the second ESD, but its severity was less than that after the first procedure. Only a few studies have reported endoscopic therapy-induced exfoliative esophagitis. We suggest that this complication may be related to imatinib-induced mucosal damage.

A 57-year-old woman was diagnosed as in the chronic myeloid leukemia-chronic phase. Imatinib mesylate(IM)was initiated at 400 mg daily. She achieved complete cytogenetic response at 3 months, and major molecular response at 10 months. IM was reduced to 300 mg daily at 12 months because of grade 1 nausea. IM was reduced to 300 mg for 5 days per week by her demand at 22 months. Major molecular response was maintained with 300 mg of IM for 3 days per week at 77 months. The intermittent IM therapy might be useful for CML patients who cannot tolerate the standard dose of IM.

The present study was designed to evaluate the incidence ofchemotherapy -induced nausea and vomiting(CINV)in patients receiving carboplatin. Chemo-naÏve patients with thoracic and gynecological malignancy, who were intended to be given carboplatin-including chemotherapy without aprepitant as antiemesis, were enrolled. CINV was assessed using a visual analog scale for a week after the final chemotherapy. Thirty-one patients were evaluated, and 6.5% and 48.4% of them developed vomiting and nausea after chemotherapy, respectively. Nausea in the delayed phase tended to be increased compared with that in the acute phase. The higher incidence of CINV was significantly correlated with younger ages(odds ratio= 0.355, 95% CI: 0.132-0.951, p=0.039). Our results indicate that further intensive antiemetic prophylaxis, such as using aprepitant or palonosetron, should be considered in patients receiving carboplatin.

In the outpatient cancer chemotherapy clinic of Gifu University Hospital, pharmacists contributed to the provision of safe and efficacious cancer chemotherapy as full-time staff, together with doctors, nurses and other medical staff. Since April 2010, three pharmacists have been in charge of the provision of pharmaceutical care services(PCS)to all patients. Furthermore, pharmaceutical intervention before medical examination(pre-PCS)was initiated in May 2011. As a consequence, the time spent for patient education and monitoring significantly(p<0. 001)increased from 39. 7±3. 2min/patient in 2010 to 48. 0±2. 6min/patient in 2011. The number of proposals on prescriptions also significantly increased, 2. 5 times, compared to 2010. The percentage of the acceptance of proposals was 94% in fiscal year 2011. Importantly, pre-PCS improved the control of chemotherapy-induced nausea and vomiting, peripheral neuropathy and skin rash. These results suggest that pre-PCS by pharmacists would be beneficial to progress the quality of outpatient cancer chemotherapy.

Based on the results of the X-ACT study, capecitabine has become one of the standard postoperative adjuvant chemotherapies for colon cancer. However, few studies of tolerability have been conducted in Japan.

The Guidance for Risk Management Plan(RMP)was released by the Ministry of Health, Labour and Welfare in April 2012. The RMP consists of safety specifications, pharmacovigilance plans and risk minimization action plans. In this paper, we outline post-marketing drug safety operations in PMDA and the RMP, with examples of some anticancer drugs.

A 69-year-old postmenopausal woman who was prescribed anastrozole for 10 months after surgical removal of her breast cancer, was referred to our hospital for acute renal failure. Because it was possible that her renal failure was related to her treatment with anastrozole, the treatment was immediately discontinued. After renal biopsy was performed to examine her renal failure, she was diagnosed as crescentic glomerulonephritis, probably related with the treatment of anastrozole. Twenty mg of oral prednisolone was administered daily after methylprednisolone pulse therapy(500 mg/day intravenous administration for three days). Her renal dysfunction was gradually improved. Renal dysfunction was considered to be a rare complication of anastrozole. Patients who are prescribed anastrozole should be watched carefully for the development of renal dysfunction.