Capecitabine monotherapy had activity in recurrent/metastatic nasopharyngeal carcinoma (NPC) as demonstrated previously in a small pilot study. We conducted a retrospective review of patients who received capecitabine for recurrent and metastatic NPC to further evaluate its clinical benefits.
Forty-nine patients with recurrent and metastatic NPC received capecitabine at a dose of 1–1.25 G/m2 twice daily for 14 days in 3-week cycles. Disease sites were locoregional in 29%, distant in 45% and locoregional plus distant in 26%. All except one had prior platinum-based chemotherapy for relapse or as adjunctive treatment. Median follow-up was 10 months (range: 3–41).
Treatment was generally well tolerated. Hand-foot syndrome was common and occurred in 86% (25% Grade 3). Grade 3 hematological toxicity occurred in 6%. Partial response rate was 31% (95% CI: 18%, 44%) and complete response rate was 6% (95% CI: 0%, 13%), for an overall response rate of 37% (95% CI: 23%, 50%). Median time-to-progression was 5 months and median survival was 14 months. One- and two-year survival rates were 54 and 26%, respectively. Significantly better survival was observed in patients treated for locoregional recurrence and those with severe hand-foot syndrome.
Capecitabine has single agent activity in NPC and severe hand-foot syndrome predicts favorable outcome. Based on our experience, capecitabine monotherapy should be considered in patients with recurrent/metastatic NPC.
Using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT), the clinical significance of 18F-FDG uptake was evaluated in patients with primary breast cancer.
Clinicopathological correlation with the level of maximum standardized uptake values (SUV) 60 min obtained from preoperative 18F-FDG PET/CT were examined in 152 patients with primary breast cancer. The prognostic impact of the level of SUV was explored using simulated prognosis derived from computed program Adjuvant! in 136 (89%) patients with invasive ductal carcinoma (IDC).
High SUV level was significantly correlated with tumor invasive size (≤2 cm) (P <0.0001), higher score of nuclear grade (P <0.0001), nuclear atypia (P <0.0001) and mitosis counts (P <0.0001), negative hormone receptor status (P = 0.001), high score of c-erbB-2 expression (P = 0.006), lymph node metastasis (P = 0.002), and IDC in comparison with invasive lobular carcinoma (P = 0.004). Multivariate analyses showed tumor invasive size, nuclear grade and estrogen receptor negativity were significantly correlated with SUV in primary breast cancer (P <0.0001,<0.0001, and <0.012, respectively), and nuclear grade was significantly correlated with SUV in tumors of invasive size 2 cm or less (P <0.0001). Tumors with high SUV (cutoff value 4.0) showed higher relapse and mortality rate compared to those with low SUV (P <0.0001).
High uptake of 18F-FDG would be predictive of poor prognosis in patients with primary breast cancer, and aggressive features of cancer cells in patients with early breast cancer. 18F-FDG PET/CT could be a useful tool to pretherapeutically predict biological characteristics and baseline risk of breast cancer.
Gastric cancer is the leading cause of death from cancer in Japan. In 2004, there were 50 562 deaths from gastric cancer; they accounted for 15.8% of the total number of cancer deaths. Since 1983, under the Health Service Law for the Aged, gastric cancer screening has been conducted nationwide for all residents aged 40 years and over.
On the basis of the standardized method developed for the Japanese Guidelines for Cancer Screening, the efficacies of various methods for gastric cancer screening were evaluated and the guideline was developed.
Four methods for gastric cancer screening were evaluated: photofluorography, endoscopy, serum pepsinogen testing and Helicobacter pylori antibody testing. On the basis of the analytic framework involving key questions, 1715 articles, published from January 1985 to February 2005, were selected using MEDLINE, the Japanese Medical Research Database and other methods. After the systematic literature review, 10 articles were identified as direct evidence and 49 articles as indirect evidence. The studies that evaluated mortality reduction from gastric cancer included five case–control and two cohort studies for radiographic screening. On the basis of the balance of benefits and harms, the recommendations for population-based and opportunistic screening were formulated. Gastric cancer screening using photofluorography was recommended for both screening programs. The other methods were not recommended for population-based screening due to insufficient evidence.
The guideline for gastric cancer screening guideline was developed based on the previously established method. Gastric cancer screening using photofluorography is recommended for population-based and opportunistic screening in Japan.
We previously reported that arterial infusion chemotherapy improved the response rate and survival of the patients with pancreatic cancer at advanced stages in an open trial. We conducted a Phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for advanced pancreatic cancer after vascular supply distribution via superselective embolization.
Patients were treated after arterial embolization for hemodynamic change to restrict the blood flow into the pancreas (mainly to the great pancreatic artery and the caudal pancreatic artery). Arterial infusion chemotherapy consisted of gemcitabine in doses that were increased from 600 to 1000 mg/m2 in subsequent cohorts on Day 1 plus continuous infusion of 5-fluorouracil 300 mg/m2/day on Days 1–5 every 2 weeks.
Twelve patients were enrolled. The maximum tolerated dose of gemcitabine was determined to be Level 3 (1000 mg/m2). Only very mild hematological and non-hematological toxicities were noted. The overall response rate was 33.3%. The median survival time was 22.7 (95% CI; 9.5–24.5) months and the 1- and 2-year overall survival rates were 83.3 and 25.0%, respectively.
Arterial infusion chemotherapy using 1000 mg/m2 gemcitabine on Day 1 and 300 mg/m2/day 5-fluorouracil on Days 1–5 every 2 weeks warrants a Phase II study.
We investigated the interobserver variation in the prostate target volume and the trend toward the use of diagnostic computed tomography (CT) or magnetic resonance (MR) images for treatment planning.
Twenty-five radiation oncologists were asked to draw the external contour of the prostate on CT images (0.3 cm spacing) of a patient with localized prostate cancer. They also answered a questionnaire regarding the use of diagnostic CT or MR images for the contouring.
Of the 25 physicians, 28% rarely or never referred to the diagnostic CT images. In contrast, the physicians tended to refer to the MR images more frequently. Approximately 50% of the physicians believed in the usefulness of contrast-enhanced images for the delineation of the prostate. As for the variation of the prostate contouring, the median craniocaudal prostate length was 36 mm (range, 21–54 mm), and the median prostate volume was 43.5 cm3 (range, 23.8–98.3 cm3). The interobserver variability was not significant in the duration as a radiation oncologist, the board certification status as radiation oncologists, and the number of treatment plans developed for prostate cancer during the last 1 year.
A wide variety of the definitions of the prostate was found among Japanese radiation oncologists.
As a risk classification system of metastatic germ cell tumors, the International Germ Cell Consensus (IGCC) classification was proposed in 1997 and has received broad approval. Since the IGCC classification was based on patients treated between 1975 and 1990, we aimed to investigate whether survival has improved for more recently treated Japanese patients.
We analyzed 296 patients with metastatic germ cell tumors treated at seven hospitals in Japan between 1990 and 2001. These cases are classified as good, intermediate or poor prognosis groups by the IGCC classification. The 5-year progression-free and the 5-year overall survivals were calculated for each prognosis group.
The median follow-up period of all patients was 53 months. In 227 non-seminomatous germ cell tumor cases, the 5-year progression-free survival (95% confidence interval) for good (n = 55), intermediate (n = 106) and poor (n = 66) prognosis was 96% (91–100), 71% (62–80) and 52% (39–65) (P < 0.001), respectively. The 5-year overall survival was 94% (88–100), 81% (73–89) and 61% (49–73) (P < 0.001), respectively. In 69 seminoma cases, the 5-year progression-free survival for good (n = 64) and intermediate (n = 5) prognosis was 78% (67–89) and 80% (45–100) (P = 0.98), respectively. The 5-year overall survival was 90% (82–99) and 80% (45–100) (P = 0.49), respectively.
There was a trend of increase in survival for any risk groups and, in particular, large increase in survival for patients with a poor prognosis. This increase is most likely attributed to more effective chemotherapy regimens and more extensive care in the experienced institutes.
To reduce cancer mortality, effective screening should be implemented properly. In Japan, the Research Group for Cancer Screening developed screening guidelines; however, the development process was not well established.
Based on the development processes of other guidelines, an original method, unique to Japan, was established to develop the Japanese cancer screening guidelines.
The guideline development process involved the following steps: topic selection, development of the analytic framework, systematic literature review, translation to recommendations, consultation and publication. Mortality reduction related to cancer screening was evaluated using both direct and indirect evidence. To select appropriate articles, an analytic framework for cancer screening program with key questions was developed. Direct evidence was defined as a single body of evidence that established the linkage between screening and health outcomes such as mortality and incidence. The use of indirect evidence to determine the level of evidence was limited to situations where test accuracy could be compared with that of a method whose evidence was supported by randomized, controlled trials. Eight levels of evidence were defined based on the study design and quality. The benefits of each screening modality were determined based on the level of evidence according to the results of the systematic review. Balancing the benefits and harms, five grades of recommendation were formulated for population-based and opportunistic screening. After organized consultations, three types of guidelines were published.
We developed a unique, standardized method for developing cancer screening guidelines in Japan. Based on this process, previously developed cancer screening guidelines have been revised.
We prospectively investigated the efficacy of opioid rotation from oral morphine to oral oxycodone in cancer patients who had difficulty in continuing oral morphine treatment because of inadequate analgesia and/or intolerable side effects.
Twenty-seven patients were enrolled and 25 were evaluated. The rate of patients who achieved adequate pain control, which provided an indication of treatment success, was evaluated as primary endpoint. The acceptability and pharmacokinetics of oxycodone were evaluated in addition to the assessment of analgesic efficacy and safety during the study period.
In spite of intense pain, the morphine daily dose could not be increased in most patients before the study because of intolerable side effects. However, switching to oral oxycodone allowed ~1.7-fold increase as morphine equivalent dose. Consequently, 84.0% (21/25) of patients achieved adequate pain control. By the end of the study, all patients except one had tolerated the morphine-induced intolerable side effects (i.e. nausea, vomiting, constipation, drowsiness). Common side effects (>10%) that occurred during the study were typically known for strong opioid analgesics, and most were mild to moderate in severity. A significant negative correlation between creatinine clearance (CCr) value and the trough concentrations of the morphine metabolites was observed. On the other hand, no significant correlation was found between CCr value and the pharmacokinetic parameters of oxycodone or its metabolites.
For patients who had difficulty in continuing oral morphine treatment, regardless of renal function, opioid rotation to oral oxycodone may be an effective approach to alleviate intolerable side effects and pain.