Reasons for avoidance of bevacizumab with first-line FOLFOX for advanced colorectal cancer.

BACKGROUND: The addition of bevacizumab to standard chemotherapy has significant clinical benefits in metastatic colorectal cancer. However, its use is often avoided due to patient condition or disease status. METHODS: Of 228 consecutive patients receiving first-line FOLFOX-based regimens from June 2007 to June 2009, 96 patients (42 %) received FOLFOX alone without bevacizumab. We retrospectively examined the reasons why bevacizumab was not combined with FOLFOX. RESULTS: Among 96 patients for whom the addition of bevacizumab was avoided, 73 patients (76 %) had bevacizumab-related contraindications including hypertension, proteinuria, bleeding, thromboembolic events, wound-healing complications and gastrointestinal perforation. Other avoidance reasons were conditions precluding the use of bevacizumab in 15 patients (16 %), economic problems and anxiety about adverse events in 8 patients (8 %), and unknown reasons in 3 patients. CONCLUSIONS: Bevacizumab-related contraindications were the main reason for drug avoidance, though economic problems and anxiety about rare but serious adverse events were also factors for avoidance of bevacizumab.

Gender difference in hematological toxicity among lung cancer patients receiving amrubicin monotherapy.

BACKGROUND: Severe hematological toxicity has been frequently observed during amrubicin monotherapy for patients with lung cancer despite the favorable anti-tumor response. The purpose of this retrospective study was to identify pretreatment factors associated with severe hematological toxicity. METHODS: The medical records of lung cancer patients treated with amrubicin monotherapy were reviewed, and univariate and multivariate analyses were conducted. RESULTS: From January 2003 to December 2006, the medical records of 103 patients were extracted. Grade 4 neutropenia was frequently observed in females (male, 66% and female, 90%, P = 0.036 in a univariate analysis). In a multivariate analysis, female gender (P = 0.019), body weight loss (P = 0.021) and amrubicin dose (P = 0.028) were significantly correlated with Grade 4 neutropenia. CONCLUSION: Gender could be considered as one of the important predictive factors associated with Grade 4 neutropenia in patients receiving amrubicin monotherapy.

Significant association between hand-foot syndrome and efficacy of capecitabine in patients with metastatic breast cancer.

Capecitabine, an oral prodrug of 5-fluorouracil (5-FU), is a promising treatment for colorectal, breast and gastric cancers, but often causes hand-foot syndrome (HFS), the most common dose-limiting toxicity. The current study was conducted to investigate the relationship between HFS and efficacy of capecitabine in 98 patients with metastatic breast cancer. Possible associations between HFS and efficacy endpoints, including time-to-treatment failure (TTF), tumor response in metastatic lesions and changes in tumor markers, were investigated retrospectively using electronic medical records. The TTF of group with HFS of grade 1 and ≥2 was significantly longer than that of group with no HFS, respectively (hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.18-0.87 for group with grade 1; HR, 0.42, 95% CI, 0.19-0.90 for group with grade ≥2). Significantly higher disease control rates for the liver metastasis were observed in patients with HFS (grade 1 and greater) than in those without HFS (92.9 vs. 42.9%, p=0.009). Furthermore, prevention of increases in tumor marker levels (carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3) and National Cancer Center-Stomach-439 (NCC-ST439)) was evident in patients with HFS. This study clearly showed a significant correlation between HFS and some efficacy markers of capecitabine therapy in patients with metastatic breast cancer, and suggests that early dose adjustment based on severity of HFS might improve efficacy. Studies are needed to explore predictive biomarkers for HFS/efficacy, so that capecitabine therapy can be further tailored to patient response.

[Retrospective study on intravenous compound injection of cancer pain patients with oxycodone and hydrocotarnine preparation in comparison with subcutaneous administration].

In Japan, although oral oxycodone is widely used for cancer pain treatment, there is no injection preparation of oxycodone used as a single ingredient. Only the compound injection of oxycodone and hydrocotarnine has received approval. Subcutaneous administration of the drug is approved, but there are few efficacy and safety reports about its intravenous administration. We compared 245 patients(187 intravenous administration patients and, 58 subcutaneous administration patients)to whom the compound injection of oxycodone and hydrocotarnine was administered from April, 2008 to September, 2011, in order to investigate the drug's efficacy and safety. The reasons for injection were the impossibility of oral administration in 105 patients, a need for dose adjustment in 56 patients, and that other drugs were not as effective in 37 patients, and side effect reduction in 33 patients. The average change in the numeric rating scale(0-10)was 3. 7→1. 8 in intravenous administration, and 3. 4→1. 2 in subcutaneous administration. The incidence of main adverse events(intravenous administration/subcutaneous administration)were constipation(37%/28%), vomiting(31%/34%), and somnolence(52%/50%). There was no significant difference in efficacy and safety. The conversion ratio differed in a case due to a change, and about 20 to 40% of addition was needed within four days after the start. It is considered that compound injection of oxycodone and hydrocotarnine is effective for cancer pain treatment.

[Survey on oncologists-provided information on treatment-related infertility to breast cancer patients].

PURPOSE: Treatment-related infertility is an important issue facing breast cancer survivors of childbearing age. A previous study at the National Cancer Center Hospital between 2000 and 2004 analyzed 136 postoperative breast cancer patients under 40 years old, and found that only 7% of them had been provided with information on fertility-related issues by their treating physicians. However, the way in which information is shared may have changed, given the recent publication of national and international guidelines on fertility issues in cancer patients, and we hypothesized that there will be an increase in the percentage of cases in which information about fertility-related issues is provided. METHODS: We retrospectively analyzed patients 40 years old or younger who underwent surgery for primary breast cancer in this hospital between 2007 and 2009. We assessed patients' and oncologists' backgrounds, pathological stage, treatment plans, and whether or not oncologists provided explanations regarding fertility-related issues. RESULTS: One hundred cases were analyzed. Five percent, 15%, and 80%of patients were < 30, 30-35, and $gt;35 years old, respectively. Sixty-one percent of patients had partners, while 29%had prior deliveries. Information on fertility-related issues was provided to 56% of patients. Significant factors influencing whether information was provided were patients' reproductive history (odds ratio(OR): 5. 717, 95% confidence interval(CI): 1.752- 18.66, p=0. 004) and recommended treatment(OR: 24.22, CI: 3.150-186. 2, p=0. 017). By contrast, oncologists' background( specialty, gender, and duration of career as a physician)was not significant. The frequency with which treatment plans were changed did not correlate statistically with the provision of information on fertility-related issues. CONCLUSIONS: Information on treatment-related infertility is now provided much more frequently than in the past. We should encourage both patients and medical professionals to increase their awareness about this important issue.

Pharmacokinetic and pharmacodynamic study on amrubicin and amrubicinol in Japanese patients with lung cancer.

PURPOSE: The pharmacokinetic (PK)-pharmacodynamic (PD) relationship of amrubicin and its active metabolite, amrubicinol, has only been evaluated using trough levels of these agents since the full PK profiles not yet been clarified so far. This study was performed to analyze the full PK profiles of amrubicin and amrubicinol and to evaluate their toxicity-PK relationships in Japanese patients. METHODS: Amrubicin (35-40 mg/m(2)) was administered to 21 lung cancer patients on days 1-3 every 3-4 weeks. Fourteen blood samples were obtained per patient over the course of 3 administration days. The plasma concentrations of amrubicin and amrubicinol were quantitated by HPLC, and the relationships between PK parameters of these compounds and hematological toxicities were evaluated. RESULTS: The overall PK profiles of amrubicin and amrubicinol were well characterized using a 3-compartment model and a 1-compartment model with a first-order metabolic process, respectively. The major toxicities were hematological. The clearance of amrubicinol was significantly correlated with grade 4 neutropenia (P = 0.01). The percentage decreases in the neutrophil count, hemoglobin level and platelet count were well correlated with the amrubicinol AUC. CONCLUSION: The pharmacokinetic profiles of amrubicin and amrubicinol were clarified, and the subsequent PK-PD analyses indicate that the clearance of amrubicinol is the major determinant of neutropenia.

Simple and sensitive HPLC method for determination of amrubicin and amrubicinol in human plasma: application to a clinical pharmacokinetic study.

A simple and sensitive high-performance liquid chromatographic (HPLC) method was developed for determination of amrubicin and its metabolite amrubicinol in human plasma. After protein precipitation with methanol without evaporation procedure, large volume samples were injected and separated by two monolithic columns with a guard column. The mobile phase consisted of tetrahydrofuran-dioxane-water (containing 2.3 mM acetic acid and 4 mM sodium 1-octanesulfonate; 2:6:15, v/v/v). Wavelengths of fluorescence detection were set at 480 nm for excitation and 550 nm for detection. Under these conditions, linearity was confirmed in the 2.5-5000 ng/mL concentration range of both compounds. The intra- and inter-day precision and intra- and inter-day accuracy for both compounds were less than 10%. The method was successfully applied to a clinical pharmacokinetic study of amrubicin and amrubicinol in cancer patients.