Estracyt(R) is an antimitotic drug used for the treatment of prostate cancer, and its most common adverse effects are nausea and vomiting. In this study, we investigated the effect of a 5-HT3 receptor antagonist, granisetron, on emesis induced in ferrets by estramustine phosphate sodium (EMP), the active ingredient of Estracyt. To clarify the mechanism of action of EMP-induced emesis, we also investigated the effect of EMP on the release of serotonin (5-HT) in the isolated rat ileum. EMP (3 mg/kg, per os) induced 75.3+/-10.2 retching episodes and 7.5+/-1.3 vomiting episodes during a 2-h observation period. The latency to the first emetic response was 58.0+/-13.5 min. Granisetron (0.1 mg/kg, per os) administered 1 h before the administration of EMP reduced the number of EMP-induced retching and vomiting episodes to 1.3+/-1.3 and 1.0+/-1.0, respectively, and prolonged the latency by a factor of almost two. EMP (10-5 and 10-4 M) increased 5-HT release from isolated rat ileum, and 10 -7 M granisetron almost completely inhibited the increase induced by 10-4 M EMP. These results suggest that EMP induces nausea and vomiting via 5-HT release from the ileum, and that 5-HT3 receptor antagonists may be useful to prevent gastrointestinal adverse effects that occur during treatment with Estracyt.

A 52-year-old woman with advanced non-small cell lung cancer was admitted to our hospital with melena and palpable purpura which appeared on her lower legs. She had been taking gefitinib for about 2 months before admission. A skin biopsy revealed leukocytoclastic vasculitis in the superficial dermis and immunofluorescence also showed the presence of C3 depositions within the blood vessel walls, which led to a diagnosis of Henoch-Schönlein purpura. The purpura gradually improved with topical steroids and bed rest; however, gefitinib had to be discontinued because of a growing papulopustular rash with intense itching, and as a result of the discontinuation, both types of skin lesions resolved. Two months later, she resumed gefitinib treatment since her level of CEA began to rise. Even though the papulopustular rash developed after the readministration of gefitinib, there had been no evidence of Henoch-Schönlein purpura recurrence during 2.5 years follow-up. It has been reported that adult onset Henoch-Schönlein purpura is often associated with malignancy. This case, however, suggests that not only drug eruption but also paraneoplastic vasculitis should be considered in the differential diagnosis of palpable purpura in patients with non-small cell lung cancer receiving treatment with gefitinib.

Adverse events associated with bevacizumab (BV) were haemorrhage, impaired wound healing and arterial thromboembolism. We report 2 patients with colorectal cancer who underwent percutaneous coronary intervention (PCI) for unstable angina soon after administration of chemotherapy including BV. CASE 1: A 74-year-old male with rectal cancer and simultaneous liver metastases was admitted to our hospital for unstable angina. Before admission he had received 4 courses of chemotherapy including BV. He had no coronary risk factors besides old age. Since coronary angiography (CAG) revealed significant stenosis in the mid-left circumflex coronary artery, PCI with a coronary stent was performed without any complications. CASE 2: A 67-year-old male with colon cancer and liver and lung metastases was referred to our Dept. of Internal Medicine for unstable angina. Before referral, he had undergone 28 courses of chemotherapy including BV. He had a history of familial hyperlipidemia and smoking. Since CAG revealed significant stenoses in the proximal left anterior descending coronary artery, PCI with coronary stents was performed without any complications. These 2 patients had no angina after PCI. PCI with coronary stent was safely performed in this patient with unstable angina soon after administration of chemotherapy including BV.

Gefitinib and erlotinib are commercially available epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) that are widely used for the treatment of non-small-cell lung cancer (NSCLC). Acute severe liver injury, although rare, has been observed in patients receiving these EGFR-TKIs. Some studies have reported that erlotinib treatment does not cause severe liver toxicity in patients with NSCLC who previously presented with severe liver injury during the course of gefitinib treatment. We retrospectively assessed the occurrence of liver toxicity in patients with NSCLC who were receiving erlotinib and had previously presented with severe gefitinib-induced liver injury.Severe liver injury occurred in only 1 of the 8 patients receiving erlotinib treatment. In this case, erlotinib was discontinued because of the onset of grade 3 skin rash and liver injury. After liver function was restored, erlotinib (100 mg) was administered at a lower dose; nonetheless, grade 4 liver injury occurred. Our findings suggest that it is necessary not only to explain the early symptoms of liver toxicity to patients who are receiving erlotinib treatment and have previously experienced gefitinib-induced severe liver injury but also to more closely monitor liver function.

Two molecular targeted drugs, sorafenib and sunitinib, were approved for treatment against advanced renal cell carcinoma in 2008 in Japan. These two drugs can be orally administered as different from interferon-alpha administered subcutaneously or interleukin-2 intravenously. In the near future, everolimus will also be approved in Japan. Moreover, other vascular endothelial growth factor receptor inhibitors will be up available. Molecular targeted drugs are associated with different adverse events from classical anticancer drugs. Control of adverse events is important to obtain maximum effectiveness of these molecular targeted drugs. Neoadjuvant therapy with these drugs for unresectable primary tumor or large tumor in solitary kidney may also be effective to complete nephrectomy or nephron spearing surgery. Treatment strategy for advanced renal cell carcinoma has been changing dramatically after introduction of these molecular targeted drugs.

Oral fluoropyrimidines, such as uracil plus tegafur (UFT), S-1 and capecitabine, have been developed and evaluated in the treatment of colorectal cancer. Their efficacy and safety are not inferior to infusional FU regimens. They provide more convenient therapy and better QOL. Careful observation and management of adverse events to preserve treatment compliance is important.

There have been few case reports of 3rd-line chemotherapy for gastric cancer. So we reported the results of CPT-11 therapy as the 3rd-line chemotherapy for gastric cancer.

We retrospectively investigated amrubicin hydrochloride(AMR)monotherapy as second or thirdline chemotherapy for small-cell lung cancer(SCLC)and assessed its efficacy and safety. AMR was intravenously administered at 25-45mg/m2 for 3 consecutive days every 3-4 weeks. Fifty-three patients were enrolled. Response rates and median survival times were as follows: total cases, 32% and 7. 4 months; sensitive relapse cases, 64% and 16. 4 months; refractory relapse cases, 27% and 5. 9 months. Neutropenia was major toxicity(Grade 3 or 4 was observed in 72% of the subjects), whereas nonhematologic toxicities were mild. Treatment with AMR appeared effective in SCLC patients previously treated with chemotherapy. On the other hand, it must be used carefully because of its relatively severe hematologic toxicities.

The electrolyte imbalance in advanced cancer patients, including hyperkalemia, hypercalcemia and hyponatremia, can be induced by various factors. Hyperkalemia is occasionally induced by chemotherapy for very large malignant tumors, due to tumor lysis syndrome. Hypercalcemia and hyponatremia are often observed in patients with breast cancer, renal cancer, prostate cancer, and the like, as a paraneoplastic syndrome. Some part of hypercalcemia results from osteolysis, but the majority is induced by hormonal factors, such as parathyroid hormone-related protein. One of the paraneoplastic causes of hyponatremia is antidiuretic hormone-producing tumor. These disorders could be morbid or even motile, resulting from encephalopathy or arrhythmia in some cases. However, it should be kept in mind that they could be improved or cured by prompt treatment. Recently, after approval of the molecular targeted drugs for epidermal growth factor receptors, such as cetuximab and panitumumab, the incidence of hypomagnesia with use of these monoclonal antibodies, is relatively frequent. In addition, small molecular targeted drugs, such as m-TORinhibitors and ABL kinase inhibitors, also exert adverse reactions including hypomagnesia and hypophosphatemia. Careful monitoring of the serum concentration of magnesium and phosphate ions, to which little attention was paid previously, is a key issue in these cases.

Recent developments in chemotherapeutic regimens have improved overall and progression-free survival in patients with various malignancies. Supportive care accompanied by antiemetic treatment is crucial for successful chemotherapy. Hence, high-level evidence with regard to antiemetic therapy is essential to create awareness among oncologists. This study reviewed evidence from clinical trials involving antiemetic therapy in Japanese patients with malignancies, and established an antiemetic guideline for oncologists in Japan. Here, we introduce the outline of this antiemetic guideline.

The ubiquitin-proteasome pathway plays an important role in the regulation of cellular proteins with regard to cell cycle control, transcription, apoptosis, cell adhesion, angiogenesis and tumor growth. Proteasome inhibition is a novel approach to the treatment of solid tumors. Bortezomib is the first proteasome inhibitor evaluated in clinical trials. In vitro experiments have shown that bortezomib treatment has a cytotoxic effect on various breast, colorectal, ovarian, pancreatic, prostate, lung and oral cancer cells. Here, the usefulness of proteasome inhibitor for cancer therapy is discussed, and a review of preclinical and clinical studies on proteasome inhibitors alone and in combination with conventional chemotherapy is included.

Mammalian target of rapamycin (mTOR) protein complex functions as an integration center for various intracellular signaling pathways involving proliferation, cell survival, and angiogenesis. These pathways are frequently abnormally regulated in cancer. Notably, Akt is an upstream molecule which is over-expressed and/or activated in several cancers. Therefore, mTOR inhibitors can be options for the treatment of cancers. At present, mTOR inhibitors are applied to treat patients with metastatic renal cell carcinoma (RCC). Temsirolimus is indicated as the first line therapy for RCC patients with poor prognosis, whereas everolimus as the second line for those refractory to sorafenib or sunitinib. Interstitial pneumonia is the most serious adverse event for both agents. Clinical trials are under way to explore indications for various cancers.

Antiangiogenesis therapy with bevacizumab demonstrated better response rate, progression free survival and overall survival in various kind of tumors including colon, breast, lung and renal cancer. It mainly potentiates antitumor activity of cytotoxic drugs. Problems remain in high cost of antibody and adverse events such as hypertension and bleeding. Small molecules of VEGF-TKI could not show survival benefit by many randomized controlled trials except for renal and hepatic cancer.

A 70-year-old man received pancreaticoduodenectomy for bile duct cancer and had been administered gemcitabine for 1 year as adjuvant chemotherapy. He complained of shortness of breath on effort and was admitted for gemcitabine-induced interstitial pneumonitis. His respiratory status was worsening after admission, so he was transferred in the intensive-care unit and required mechanical ventilator and steroid pulse therapy with 1,000 mg/day of methylprednisolone. His symptoms and radiological findings were dramatically improved. The patient could be discharged on the 24th day after admission. Interstitial pneumonitis induced by gemcitabine is rare, but could lead to severe complications, which could develop after long-term administration and should be treated by corticosteroid as soon as possible.