After 1990's, the development of new generation anti-cancer agents produced encouraging improvement of prognosis in inoperable or relapsed stomach cancer and colorectal cancer. However, non-hematological toxicity, such as peripheral neuropathies, become a new dose-limiting toxicity. In several new generation drugs, measures for controlling peripheral neuropathy had not been established besides dose modification or schedule modification. We tried to control the peripheral neuropathy induced by anti-cancer agents with the assistance of an adjuvant analgesics ladder. A total of 18 digestive cancer patients who presented with peripheral neuropathy of grade 1 or more(NCI-CTCAE ver 3.0), in the chemotherapy including Taxol or Oxaliplatin, were enrolled. The first stage of the adjuvant analgesics ladder was set as the antidepressant(amoxapin), the second stage was anticonvulsive drugs(valproic acid or clonazepam) and the third stage was antiarrhythmic drug(mexiletine). In each stage, if the drug turned out to be ineffective after two / weeks follow-up, it shifted to the next stage. The response rate of each step was 61.1%(11/18)of the first stage, 50.0%(5/10)of the 2nd stage, 50.0%(2/4)of the 3rd stage, and the overall response rate was 77.8%. The discontinuance of cancer treatment by peripheral neuropathy was observed only in 1 patient 5.5%(1/18)in the Taxol administered group. The toxicity profile was skin eruption and drowsiness, but the skin eruption was observed only in 1 patient at the 3rd stage and the drowsiness in 2 patients at the 2nd stage. It appears that the method to control the peripheral neuropathy induced by anti-cancer agents with the assistance of adjuvant analgesics ladder was effective and safe, but a large-scale clinical trial was warranted.

Subjects were 239 patients with colorectal cancer who underwent curative resection surgery from December 1994 to March 1997(Stage I-III b). The patients were given 5'-DFUR for postoperative 10 months as scheduled. They had been allocated into either a 1-year group or a 3-year group by dynamic randomization. 5'-DFUR was administered by an intermittent regimen such as 1,200 mg/body/day for five days followed by two days rest. All patients were followed for five years at least.

Biomarkers for lung cancer may be used for early detection, diagnosis, treatment selection and prognostication. They are also expected to contribute to the realization of tailored therapy. To identify the optimal therapy candidates, EGFR (epidermal growth factor receptor)mutations are biomarkers available as predictive factors for EGFR tyrosine kinase inhibitors and UGT(uridine diphosphate glucuronosyltransferase)1A1 as a risk predictor of irinotecan in the present practice. Novel potential biomarkers for prognostication have been developed by genomic methods. Biomarker development for early detection is much awaited for the future.

Prognostic, predictive and safety biomarkers of chemotherapy for colorectal cancer have been reported. Recently, it was reported that KRAS mutation was present in 27-43% of patients, was associated with resistance to antibody against the epidermal growth factor receptor(EGFR), and showed a poorer survival in metastatic colorectal cancer. The search for biomarkers is therefore being conducted vigorously in parallel with a number of clinical trials that are currently being conducted for new drugs. We believe that future areas of research will include the establishment of clinical evidence through large-scale clinical trials and the standardization of analysis protocols.

Bevacizumab, a humanized monoclonal antibody to VEGF for advanced recurrent colorectal cancer, has been known for complications of gastrointestinal perforation, hemorrhage, thromboembolism and proteinuria, as adverse effects. These findings must be taken care as well as adverse drug reactions (ADR) caused by combination chemotherapy. We here in present a clinical experience in treatment with bevacizumab for unresectable colorectal cancer. Six patients treated with bevacizumab for over two courses until April 2008 were analyzed for this study. PR was obtained in one case with mFOLFOX6. Even though, grade 3 neutropenia was observed in only one case with FOLFIRI, the other cases had grade 2 or less in ADR. In addition, there were no any specific ADRs related with bevacizumab, so we concluded that combination chemotherapy for advanced recurrent colorectal cancer with bevacizumab was well-tolerated.

We are performing a phase I clinical trial of combination-therapy with gemcitabine and epitope peptide derived from human vascular endothelial growth factor receptor (VEGFR) for advanced pancreas cancer. The aim of this study was to evaluate the safety, immunological response and tumor response. Six patients have been enrolled at present. During the clinical course, no major adverse events were observed. Additionally, two out of 6 cases showed a minor shrinkage of the tumor. Immunological response has not been analyzed yet. These results indicated that a combination-therapy with gemcitabine and epitope peptides derived from VEGFR could be tolerable.

We present a case of hand-foot syndrome (HFS) induced by bolus 5-fluorouracil (5-FU) therapy. A 54-year-old man received bolus 5-FU for adjuvant treatment of rectal cancer. After second cycle, he presented to the clinic with a rash on the both palms accompanied by symptoms of pain, erythema, swelling, and desquamation consistent with grade 2 HFS. HFS appears more frequently with 5-FU delivered by continuous infusion or with the 5-FU oral derivative capecitabine than with bolus 5-FU therapy. HFS is a leading cause of treatment interruption which may impact on the efficacy of the treatment regimen. This possibility must be considered when patient is receiving a bolus 5-FU treatment, and effective and appropriate patient education is an essential part of management to prevent progression to a more severe grade of toxicity by early detection of HFS.

A 69-year-old female patient with type 2 advanced gastric cancer (s-T4N0M0H0Cy0P0, f-Stage IIIA) located from lower corps to antrum underwent a distal gastrectomy with D2 lymphandectomy in May 2006. After surgical treatment, S-1+ docetaxel combined chemotherapy was started for pEM (+) due to direct invasion to pancreas head as the first-line chemotherapy. However, the local recurrence whose diameter was 24 mm at pancreas head was detected with enhanced CT in December 2006. Moreover, nevertheless CPT-11+CDDP combined chemotherapy or paclitaxel monotherapy as the second or the third-line chemotherapy, respectively, the diameter of the local recurrence enlarged to 38 mm in November 2007. Therefore, chemo-radiotherapy using with S-1 and CDDP was started in December 2007 and the diameter of local recurrence was reduced to 25 mm in January 2008. No adverse event of grade 3 or more occurred during chemo-radiotherapy except for grade 3 of neutropenia. Chemo-radiotherapy for this gastric-cancer patient with local recurrence of multiple anti-tumor drug resistance was effective and safe.

We reviewed 7 cases of clinical record with preoperative chemo-radiotherapy to evaluate the clinical effectiveness of the chemo-radiotherapy for T4 rectal cancer. The preoperative radiation therapy consisted of 40-45 Gy delivered in fractions of 1.8-2.0 Gy per day, five days a week. A treatment of 5-fluorouracil, 500 mg/body per day intravenously, or oral UFT-E (300 mg/m2) with l-leucovorin (75 mg) per day, or oral S-1 (80 mg/m2) per day five days a week, was given during radiotherapy. Grade 1 or 2 adverse effects occurred in 3 patients during chemo-radiotherapy, but the completion of chemo-radiotherapy was achieved in all of the 7 patients. Tumor invasion identified by CT and MRI to other organs in the pelvis disappeared in four cases with complete or partial response after a month of chemo-radiotherapy. Although the other organs were also removed during surgery in 4 patients, curative surgery was performed in 5 patients. There was no histological invasion seen to other organs in 4 patients, and one patient had histological complete disappearance of tumor. Although complications after surgery were found in all of the patients, they were improved by conservative treatment. One of 4 patients with curative surgery had liver and local recurrence, but others survived without recurrence. Preoperative chemo-radiotherapy was expected to be a safe and effective treatment to improve the resection rate and prognosis for T4 rectal cancer.

We investigated the clinical significance of chemo-radiotherapy (CRT) and chemotherapy (CT) in patients with primary metastatic esophageal cancer.

We have used glutathione for prevention of oxaliplatin-related neurotoxicity with reference to the article of Cascinu et al. We investigated oxaliplatin-related neurotoxicity in Kariya Toyota General Hospital(KTGH)and compared with the data described in the article of Gamelin about the severity of its neurotoxicity. Grade 3 neurotoxicity was observed in only 5 of 44 patients(11.4%). The median number of cycles and cumulative dose of oxaliplatin were 12 cycles(5-27 / cycles)and 802.2(273.2-1,952.4)mg/m(2), respectively, at Grade 3 neuropathy. We evaluated retrospectively neuro-toxicity grade at cumulative oxaliplatin doses of approximately 500-520 mg/m(2). The severity of neurotoxicity observed in KTGH was significantly lower than in the group without Ca/Mg. We found no difference between the group with glutathione and / with Ca/Mg. Glutathione infusions seemed to prevent oxaliplatin-related neurotoxicity.

Recently, the ASCO guideline has added TLS. Prevention and recognition of the disease and state are important. Molecular targeting drugs, small molecule tyrosine kinase inhibitors and monoclonal antibodies induced rapid regression of the tumors and carry a risk of TLS. The recognition of the disease which may have a high risk of TLS and laboratory TLS is important.

We report that team-based medical care has an important role in tailor made chemotherapy for colorectal cancer. We organized a chemotherapy support team to facilitate the early detection of toxicity and to get hold of therapeutic needs in individual patients. We also measured the circadian variation of 5-fluorouracil plasma concentrations to permit tailor dosed chemotherapy. To date, the chemotherapy support team has managed the performance of pharmacokinetic modulating chemotherapy in 30 patients with unresectable or recurrent colorectal cancer. The median survival time was 19 months after the first-line chemotherapy and 14 months after the second-line treatment. Our results suggest that team-based medical care is practically useful for tailor made chemotherapy in patients with colorectal cancer.

Case1 was a 52-year-old man who had recurrence of postoperative intra-abdominal disseminations from gastrointestinal stromal tumor (GIST) of the jejunum. Case2 was a 66-year-old man who had GIST of the jejunum with multiple liver metastases. Two cases presented hemoperitoneum caused by administration of imatinib mesylate, and we conducted emergent surgery. In spite of surgically non-curative cases, it is suggested that the surgical management for GIST of high grade group with peritoneal exposure should be followed by the administration of imatinib mesylate.

Falls among the elderly mainly result from aging, lack of exercise, and physical and/or mental disorders. They cause fractures and other injuries. It is necessary that likelihood of falling should be evaluated from the view point of both decreased physical function and fear of falling. General exercise including balance training is considered to be most effective to reduce falls. We must take good care not to cause falling and resultant fracture due to exercise of falls prevention program. Many sided intervention, including a check and counseling on medication and environmental improvement, walking in the sunshine, which stimulates vitamin D biosynthesis and so on, are needed. Further studies on falls prevention among the elderly with dementia and males receiving hormonal therapy with prostatic cancer are necessary.

The major toxicities associated with paclitaxel(PTX)-based chemotherapy are myelosuppression, peripheral neuropathy and myalgia/arthralgia. In the present study, a retrospective study was carried out to compare the incidence of adverse events during PTX-based chemotherapy between 58 cases treated every 3 weeks(tri-weekly regimen)for breast cancer and non-small cell lung cancer and 47 cases with weekly regimen for breast cancer and gastric cancer. Hematological toxicity such as neutropenia and thrombocytopenia, peripheral neuropathy and myalgia/arthralgia occurred more frequently in patients with a tri-weekly regimen than in those with a weekly regimen(grade 3/4 neutropenia: 65.5% versus 12.8%, odds ratio; 12.98, grade 2/3 peripheral neuropathy: 24.1% versus 6.4%, odds ratio; 4.67, and grade 2/3 myalgia/arthralgia: 43.1% versus 4.3%, odds ratio; 17.05). The development of peripheral neuropathy and myalgia/arthralgia was dependent on the dose per injection, but not on the cumulative dose of PTX. The initial onset of peripheral neuropathy and myalgia/arthralgia was observed in more than 80% of patients during the first course of the tri-weekly regimen, while it was seen in any course of the weekly regimen. The incidence of other nonhematological adverse events was not different between the two regimens except for nausea. Our present findings suggest that the peripheral neuropathy and myalgia/arthralgia are highly frequent adverse events that depend on the dose per injection of PTX, in which the incidence was more frequent in the tri-weekly than in the weekly regimen.

Vinorelbine is a newanti-cancer drug that is available for advanced or metastatic breast cancer, approved by the Japanese Ministry of Health, Labour and Welfare in May 2005. At present, we evaluated the efficacy and safety of vinorelbine in our hospital. 51 patients were treated with vinorelbine since April 1, 2006 to August 20, 2007. Average age was 55.9 years old and period of treatment was 161.9 days. Average number of previous treatments was 2.2, and 37 patients(72.6%)were treated with anthracyclines and taxanes. The response rate was 19.6%, there was one complete responder, and nine partial responders. Especially, the response rate was 16.2% in patients pretreated with anthracyclines and taxanes. The major toxicity was grade 3 or 4 neutropenia(15.7%), and superficial phlebitis(7.8%). Vinorelbine will be a standard treatment agent for patients pretreated with anthracyclines and taxanes.

We analyzed the efficacy and safety of Vinorelbine monotherapy in 18 patients with advanced or metastatic breast cancer between May 2006 and July 2007, retrospectively. The outcomes were PR in 4 cases, long-term SD in 1, SD in 5, and PD in 8. The overall response rate was 22.2%(4/18), and a clinical benefit was shown in 27.8%(5/18). The median time to progression(TTP)was 138 days. Major adverse events were leukopenia(72.2%), neutropenia(77.8%) and superficial phlebitis(58.8%). These results suggest that Vinorelbine was a safe and effective agent.