Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and distressing side effects of chemotherapy that decreases patients' quality of life and motivation for treatment. Therefore, prevention and treatment of CINV are essential for motivating patients to continue chemotherapy. International societies such as American Society of Clinical Oncology (ASCO), Multinational Association of Supportive Care in Cancer (MASCC)/European Society for Medical Oncology (ESMO), and National Comprehensive Cancer Network (NCCN) have published guidelines for using antiemetics, and these guidelines were published in Japan in May 2010. However, both the Japananese and international guidelines do not provide sufficient clinical trial-based evidence for antiemetic use in the Japanese population. In this study, we attempted to evaluate and clarify the frequency of CINV in clinical trials in Japan. We found that thet guidelines specify different emetogenic potentials of some antineoplastic agents such as gemcitabine. Therefore, we believe that it is necessary to reevaluate the emetogenic risk of such antineoplastic agents and to develop a practical and standard antiemetic therapy so that in the future, patients do not hesitate to undergo chemotherapy because of side effects.

At our hospital, we use aprepitant for nausea and vomiting when administering highly emetic anticancer agents, according to "Guidelines for the Appropriate Use of Antiemetic Agents" given by the Japan Society of Clinical Oncology. We initiated the intravenous administration of fosaprepitant for better compliance compared with aprepitant; however, we observed phlebitis after the infusion of fosaprepitant. Therefore, we investigated measures to reduce phlebitis associated with the infusion of fosaprepitant. For the first premedication, fosaprepitant (150 mg) was dissolved in 100 mL of saline and administered for 30 minutes; 1 of 2 patients showed grade 4 phlebitis. For the modified premedication, fosaprepitant, dexamethasone, and 5- HT(3) antagonist were dissolved in 100 mL of saline and administered for 30 minutes. The modified premedication was administered to a total of 27 patients; 5 patients developed mild phlebitis (grade 1), but infusion could be continued by treating their phlebitis with a hot pack. We used a combination of dexamethasone and 5-HT(3) antagonist with fosaprepitant as a modified premedication in order to avoid drug-induced vascular damage, which resulted in the pH decreasing to 6.20-7.55 (close to neutral) and a shorter infusion time.

S-1 administration for 28 consecutive days followed by 14 days of rest (6-week cycle) is often chosen as second-line chemotherapy for advanced pancreatic cancer (PC), but it causes gastrointestinal toxicity. In comparison, in gastric cancer or head and neck cancer, S-1 administration for 14 consecutive days followed by a 7-day rest period (3-week cycle) reduced gastrointestinal toxicity. This study retrospectively evaluated the efficacy and safety of a 3-week S-1 schedule compared to a 6-week schedule in patients with gemcitabine (GEM)-refractory advanced PC. Fifty-seven patients were treated with the 6- week S-1 schedule and 68 patients were treated with the 3-week S-1 schedule. There were no statistical differences in overall survival (p=0.13) and progression-free survival (p=0.190). With regard to adverse events, the rates of nausea (p<0.01) and vomiting (p=0.04) were lower with the 3-week schedule than with the 6-week schedule. Thus, S-1 therapy with a 3- week schedule as second-line chemotherapy in patients with GEM-refractory advanced PC was associated with reduced gastrointestinal toxicity and similar efficacy, when compared to a 6-week schedule.

Japan Society of Clinical Oncology published a guideline for anti-emetic therapy two years ago. This guideline was a first evidence based guideline of anti-emetic treatment for the patients who received chemotherapy in Japan. To investigate a current situation of anti-emetic treatment in Japan, we analyzed the data from nationwide questionnaire.

An increase in the number of young women with breast cancer together with improved outcomes after breast cancer treatments have lead healthcare providers and society in general to become more aware of fertility preservation. The potential for infertility caused by cancer treatment is one of the most important quality-of-life issues for young women with cancer, and guidelines and decision-aids to support those who wish to have children after cancer treatment have been developed. To move forward, a prospective database needs to be developed in order to overcome safety concerns, and to allow network building among breast oncologists and reproductive specialists. A multidisciplinary team is also urgently needed to address psychosocial and ethical issues.

Antineoplastic chemotherapy and irradiation affect gonadal function and may lead to infertility. Recovery of gonadal function is frequently observed after conventional chemotherapy in young patients with hematological malignancies, but conditioning regimens before hematopoietic stem cell transplantation result in permanent gonadal failure. Cryopreservation of sperm is effective for male patients, but it becomes difficult even after a single cycle of chemotherapy and therefore should be accomplished before starting chemotherapy. Embryo freezing after in vitro fertilization of harvested oocytes is an established method to preserve fertility in female patients. In addition, harvesting and freezing of unfertilized oocytes is also being evaluated in a clinical study. However, collection of good oocytes after chemotherapy is difficult. In addition, oocyte harvesting is an invasive procedure and may be associated with hemorrhage or infectious complications. Ovarian shielding during total body irradiation allows ovary preservation in most female patients, but this cannot be performed in patients with active malignancies. Strategies for gonadal function preservation should be planned before starting treatment for hematological malignancies.

To evaluate long-term continuous administration of docetaxel (DOC), over survival rate, PSA level and adverse effects were analyzed, retrospectively. We also compared the results of long-term treatment group and short-term treatment group.

Systemic chemotherapy based on 5-fluorouracil (5-FU) is a standard treatment for unresectable or recurrent large intestinal cancer. Although hyperammonemia is a known side effect of 5-FU that can cause serious pathological conditions, only a few cases have been reported. We describe 4 cases of 5-FU-related hyperammonemia with impairment of consciousness in patients who received 5-FU chemotherapy for large intestinal cancer with multiple liver metastases. Hemodialysis was effective in 1 severe case. There have been no detailed reports on the use of hemodialysis for hyperammonemia caused by 5-FU. Renal dysfunction is considered to be a risk factor for hyperammonemia caused by 5-FU and it is necessary to pay particular attention in patients with renal dysfunction who receive chemotherapy with 5-FU. Here we summarize our cases together with 16 previously reported cases of hyperammonemia caused by 5-FU in Japan.

We report an 81-year-old woman with multiple myeloma who developed acute cardiac injury after receiving bortezomib. The patient received weekly intravenous bortezomib. She developed shortness of breath and bilateral pedal edema on day 19. Electrocardiography showed no ST-T changes but the cardio-thoracic ratio was increased, the ejection fraction was decreased, the ventricular septum showed hypokinesis and mitral regurgitation was noted. We stopped bortezomib and started acute congestive heart failure treatment. ST-T changes were detected after the patient's condition improved. There was no evidence of coronary stenosis on CT angiography. Acute cardiac injury is rare during bortezomib administration, but patients should be monitored carefully during treatment.

After fosaprepitant (FOS)was added to the National Health Insurance drug reimbursement price list, we switched the route of administration of antiemetics from oral to intravenous in chemotherapy regimens for colon cancer to improve patient medication adherence. However, because the number of patients reporting application-site disorders after administration of FOS increased, we monitored the incidence of these disorders in patients with colon cancer to identify ways to avoid them. In our prospective study, patients receiving conventional FOS dosing regimens (control group)were compared with those receiving diluted FOS solutions (study group). There were no significant differences between the two groups with respect to the incidence of application-site disorders, and contrary to expectations, the incidence was higher in the study group than in the control group. On the basis of the principle of non-maleficence and the availability of alternative therapies using oral aprepitant (APR), we terminated this study early and adopted the basic strategy that all patients with application-site disorders, except for those with central venous access devices, should be treated with oral APR after confirming their preferences.

The efficacy and safety of nanoparticle albumin-bound paclitaxel(nab-paclitaxel)administered every 3 weeks for unresectable or recurrent gastric cancer was evaluated retrospectively. Nab-paclitaxel was intravenously administered at 260 mg/ m² on day 1 of each 21-day course without anti-allergic premedication until disease progression or discontinuation. Nine patients received nab-paclitaxel. The overall response rate was 11.1%, and the disease control rate was 55.6%. Grade 3/4 toxicities included neutropenia(44.4%), leukopenia(33.3%), and peripheral sensory neuropathy (33.3%). It is important to manage both neutropenia and peripheral neuropathy. Although only few cases were analyzed, therapeutic effect can be obtained even with the starting dose of 180 mg/m² suggesting management of toxicities will be feasible. In view of the toxicities observed, a reduced starting dose of 180 mg/m² should be considered in the case of poor performance status patients. Nab-paclitaxel is a promising drug because of its convenience and may replace weekly paclitaxel for unresectable or recurrent gastric cancer.

We report the long-term survival of a patient with metastatic hepatocellular carcinoma (HCC), successfully treated with transcatheter arterial chemoembolization (TACE)/hepatic arterial infusion chemotherapy (HAIC) combined with long-term administration of sorafenib. A 74-year-old man underwent hepatectomy for a huge hepatocellular carcinoma, measuring 19 × 13 cm. Multiple intrahepatic HCCs that recurred 5 months post-surgery were treated with TACE. After 3 cycles of TACE, however, sorafenib was administered to treat progressive disease. Six months after sorafenib treatment, TACE combined with sorafenib was administered for treatment of refractory intrahepatic lesions. Following further disease progression, TACE was replaced by up to 11 rounds of HAIC. We report successfully treatment of refractory metastatic HCC with sorafenib for more than 30 months along with a review of the literature.

A 58-year-old woman was suffering from abdominal pain due to large liver metastases(LM)and lung metastasis from sigmoid colon cancer. After laparoscopic sigmoidectomy, three 6 g/wk high dose hepatic arterial infusions(HDHAI)of5 - fluorouracil (5-FU) were administered and the tumor decreased in size. Unfortunately, the patient had an infectious pseudoaneurysm at the site of puncture. She was given a drainage and femoro-femoral(F-F)bypass. At last, a hepatectomy, radiofrequency ablation(RFA), and catheter insertion from gastroepiploic artery, were performed successfully. Subsequently, she received a half HDHAI and several systemic chemotherapy drugs. However, residual liver metastases developed thrice and we operated on all of them. Finally, when the hepatic arterial infusion(HAI)catheter became unavailable, we only continued the systemic therapy (Erbitux+FOLFIRI). However, inoperable residual liver metastases(maximum 13 cm in size)occurred. We chose to administer hepatic transarterial embolization(TAE)therapy 3 times. From the second time, we performed TAE from the right subphrenic artery and in the third time, we added 1-day HAI therapy. Finally, the tumor size decreased(maximum 9 cm). The patient is still an outpatient 5 years after the first HDHAI.

Nanoparticle albumin-bound paclitaxel (nab-PTX, Abraxane®) does not require premedication, and it can be used for patients with alcohol intolerance. We administered nab-PTX to 31 patients with breast cancer between October 2010 and April 2013. Eighteen patients had progressive, recurring breast cancers and 13 patients had locally advanced operable breast cancers. The treatment schedules were 175 or 260 mg/m² every 3 weeks (q3w). No patient experienced an allergic reaction. Grade 1-3 sensory neuropathies were observed in 20 patients; however, no patient experienced grade 4 neuropathy. In patients with locally advanced, operable breast cancer, 1 patient treated with 175 mg/m² q3w had a partial response (PR), while of the patients treated with 260 mg/m² q3w, 10 patients showed a PR, and 1 patient had stable disease (SD). Of the patients with progressive, recurring breast cancer, 2 patients showed a PR and 4 patients had SD when treated with 175 mg/m² q3w, whereas 1 patient displayed a PR and 1 patient had SD when treated with 260 mg/m² q3w. Our investigation suggests that nab-PTX is well tolerated, even by patients with advanced breast cancer.

We examined the treatment condition; adverse events, especially hand-foot syndrome (HFS); and prognosis in 65 patients with colon cancer who received adjuvant chemotherapy with capecitabine. The treatment completion rate was 75.4%; however, only 15.4% of patients completed treatment without dose reduction or treatment interruption. HFS occurred in 78.5% of all cases. The 3-year relapse-free survival rate was 73.8% for all cases, 80.8% for treatment-completed cases, and 51.1% for treatment-discontinued cases; however, there were no differences in relapse-free survival rates for cases that required dose reduction or treatment interruption. We conclude that adjuvant chemotherapy with capecitabine is effective in colon cancer and that completing treatment (even with dose reduction or dose interruption) improves prognosis.

We evaluated the efficacy of intraperitoneal chemotherapy with cisplatin (CDDP) for peritoneal recurrent gastric cancer following surgical intervention. Twelve patients were enrolled. The combination systemic chemotherapy was S-1 or S-1 plus paclitaxel (S-1+PTX). PTX was administered intravenously at 80 mg/m² on day S-1 and 15. S-1 was administered at 80 mg/ m²/ day for 7 consecutive days, followed by 7 days of rest, and the cycle was repeated. CDDP was administered intraperitoneally at 40 mg/body on day 8. This treatment was repeated every 4 weeks until disease progression was diagnosed. The survival time(ST)and time to treatment failure(TTF)were estimated. The surgical interventions were gastrectomy in 3 patients, colostomy in 8 patients, and enterostomy in 1 patient. Overall, the median TTF and ST were 294 days and 455 days, respectively. When stratified by surgical method and combination chemotherapy, the median TTF and ST were not statistically significant. However, when stratified by performance status (PS), the median TTF was 352 days for patients with PS 0 and 218 days for those with PS 1, 2 (p=0.0029), whereas the median ST was 553 days for patients with PS 0 and 331 days for those with PS 1, 2 (p=0.0198). In conclusion, the data suggest that intraperitoneal CDDP chemotherapy with systemic chemotherapy is effective for the treatment of extensive peritoneal recurrent gastric cancer, especially in patients with good PS.

This review describes the secondary cancer after radiotherapy. Secondary cancer is a great concern for cancer survivors, especially for childhood cancer survivors not only because of their intrinsic high susceptibility to radiation but also because of successful achievement of longer survival. Recent advance of molecular biology reveals unique genomic changes, which distinguish radiation-induced tumors from spontaneous or chemically induced tumors.

We report a case of phenytoin intoxication caused by an interaction between phenytoin and capecitabine. A 41-year-old woman was started on phenytoin (200 mg p.o. daily) for convulsive attacks due to breast cancer brain metastasis. Three months later, chemotherapy with 2,400 mg/d capecitabine (3 weeks on and 1 week off) and 1,250 mg/d lapatinib was initiated for the treatment of breast cancer. Approximately 10 weeks after starting chemotherapy, the patient began to complain of nausea, vomiting, and unsteadiness, and she was admitted to our hospital. Since her serum phenytoin level was more than 40 μg/mL, she was diagnosed with phenytoin intoxication. Phenytoin is metabolized in the liver, primarily by the CYP2C9 isozyme, which can be competitively inhibited by capecitabine. Thus, we determined that the patient developed phenytoin intoxication due to the interaction between phenytoin and capecitabine. This indicates the importance of considering the potential drug-drug interactions while prescribing anticancer agents and antiepileptic drugs simultaneously.