International Journal of Clinical Oncology

Background. Cancer patients are at high risk of developing a second cancer after the treatment of initial cancers. Understanding the characteristics of multiple primary cancer is important to establish an effective surveillance program for the early detection of second cancers. Methods. We analyzed the cancer registry records from 1986 to 1995 at the Cancer Institute Hospital. The combination of the sites of the index and second cancers and the time intervals between the two cancers were examined. For colorectal cancer, another database of patients between 1946 and 1991 was analyzed, with special reference to synchronous and metachronous cancers. Results. Out of 24,498 registered cases, there were 1281 (5.2%) multiple cancers, of which 464 (1.9%) were in the same organs and 817 (3.3%) were in other organs. Gastric or colorectal cancer frequently developed as the second cancer regardless of the site of the index cancer. Although the majority of the second cancers developed within 3 years after the index cancer, some developed 5 years or more after the index cancer. In colorectal cancer, the cases with metachronous cancer were similar to those with hereditary nonpolyposis colon cancer. The frequent combination of an advanced index cancer and an advanced second cancer and relatively poor survival after the second cancers in the metachronous cases may reflect delayed diagnosis of the second colorectal cancer. Conclusion. Careful attention should always be paid to the second cancer in treating cancer patients. Further analysis by individual site of the index cancers is needed to construct an effective surveillance for second cancers.

Treatment modality of desmoid-type fibromatosis (DF) has changed from surgery with a wide surgical margin to conservative treatment. In this study, tumor characteristics of DF, transition of the treatment modality, and clinical outcome of surgical treatment were analyzed based on data obtained from the bone and soft tissue tumor registry established in Japan. Data were collected as registration data and follow-up data. Five hundred and thirty registered cases of DF were identified, including 223 cases with follow-up data with or without surgical treatment. The number of registered patients increased gradually. The frequency of surgical treatment was gradually reduced year by year. The 3-year local recurrence free survival (LRFS) was 77.7%, with tumor location and size tending to correlate with LRFS. Interestingly, there was no significant difference in LRFS between wide and marginal margin (P = 0.34). The treatment modality has shifted from surgical to conservative treatment, with risk factors for surgical treatment similar to those noted in previous studies. The National registry system is crucial for a rare disease such as DF, and in the future, a population based registry system should be established to better comprehend the actual status of DF.

This study was conducted to evaluate the efficacy and safety of S-1 in patients with advanced non-small-cell lung cancer (NSCLC), receiving two or more prior chemotherapy regimens. S-1 was administered orally for 14 consecutive days, followed by a 7-day rest period. This treatment course was repeated until disease progression or intolerable toxicity occurred. From 2010 to 2012, 45 patients were enrolled in this study. Of the 45 patients, 4 patients [8.9 %, 95 % confidence interval (CI) 0.6–17.2 %] exhibited a partial response and 24 patients (53.3 %) exhibited stable disease. The disease control rate was 62.2 % (95 % CI 48.1–76.4 %). Median progression-free survival was 71 days, and median survival time was 205 days. Four patients had grade 3 hematological toxicities, but toxicities of grade 4 were not observed in this study. Although S-1 monotherapy as third-line treatment or beyond was well tolerated, the response rate for this regimen did not demonstrate sufficient activity for patients with advanced NSCLC.

FOLFOXIRI is now regarded as the chemotherapy regimen that offers the best platform for the treatment of colorectal cancer. However, the safety and efficacy of FOLFOXIRI + panitumumab has not been demonstrated. We conducted a phase I study to determine the recommended dose of FOLFOXIRI + panitumumab as first-line treatment for RAS wild-type metastatic colorectal cancer (mCRC). Patients received combination therapy consisting of panitumumab (6 mg/kg on day 1) + FOLFOXIRI [irinotecan (CPT-11), oxaliplatin (L-OHP) 85 mg/m2, and folinate (LV) 200 mg/m2] on day 1, followed by fluorouracil (5-FU) 3200 mg/m2 infused as a 46-h continuous infusion starting on day 1) repeated every 2 weeks as first-line treatment of RAS wild-type mCRC patients. A decrease in CPT-11 dose was planned (started at level 1: CPT-11 165 mg/m2). Seven patients were enrolled, and six were assessed for safety and efficacy. Maximum tolerated dose was not reached at level 1; all patients were treated at these levels. The common Grade 3 or 4 relevant toxicities were diarrhea (50%), hypokalemia (33%) and stomatitis (33%). No treatment-related deaths occurred. Of the six patients assessed four had partial response and the two others had stable disease; hence, the response rate was 66.7% (95% confidence interval 28.9–100%) and the disease control rate was 100%. Time to protocol treatment failure was 7.2 (1.4–7.3) months. The FOLFOXIRI + panitumumab chemotherapy regimen was well tolerated by our patients with mCRC and showed promising anti-tumor activity. The recommended phase II dose was determined to be the same as the standard doses of this regimen used worldwide.

In the double-blind, phase 3 PALOMA-3 study, palbociclib–fulvestrant significantly prolonged progression-free survival versus placebo–fulvestrant in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (MBC) whose disease had progressed on prior endocrine therapy. The present study evaluated the efficacy, safety, and pharmacokinetics of palbociclib plus fulvestrant in Japanese patients enrolled in PALOMA-3. Pre/peri/postmenopausal women with HR+/HER2– MBC were randomized 2:1 to fulvestrant (500 mg) and either palbociclib (125 mg/day; 3 weeks on/1 week off; n = 347) or placebo (n = 174). Prespecified exploratory analyses compared the efficacy (data cutoff: October 23, 2015), safety, and pharmacokinetics (data cutoff: December 5, 2014) in Japanese women versus the overall population. A total of 35 Japanese women were randomized to palbociclib–fulvestrant (n = 27) or placebo–fulvestrant (n = 8). Median progression-free survival was 13.6 months (95% CI, 7.5–not estimable) in the Japanese palbociclib–fulvestrant group and 11.2 months (95% CI, 5.6–not estimable) in the placebo–fulvestrant group. The most common adverse event (AE) in Japanese patients was neutropenia (all grades, 93%); no discontinuations were due to an AE. Geometric mean trough concentration values (within-subject mean steady state) for palbociclib were similar for Japanese Asian (excluding Japanese), and non-Asian patients (84.4 ng/mL, 86.3 ng/mL, and 74.8 ng/mL, respectively). The results for the overall population and Japanese patients in PALOMA-3 suggest that palbociclib plus fulvestrant was effective and well tolerated in Japanese patients with HR+/HER2‒ MBC whose disease had progressed on prior endocrine therapy (Pfizer; NCT01942135).

The aim of the study was to evaluate the performance of “Acute Physiology and Chronic Health Evaluation II” (APACHE-II), “Simplified Acute Physiology Score 3” (SAPS-3), and “APACHE-II Score for Critically Ill Patients with a Solid Tumor” (APACHE-IICCP) models in cancer patients admitted to ICU. Prospective cohort study of 414 patients with an active solid tumor. Discrimination was assessed by area under receiver operating characteristic (AROC) curves and calibration by Hosmer–Lemeshow goodness-of-fit C test (H–L). The hospital mortality rate was 32.6%. In the total cohort, discrimination for prognostic models were: APACHE-IICCP (AROC 0.98), APACHE-II (AROC 0.96), SAPS-3 for Central and South American countries (SAPS-3CSA) (AROC 0.95), and SAPS-3 (AROC 0.91). Calibration was good (p value of H–L test > 0.05) using APACHE-IICCP, APACHE-II and SAPS-3CSA models. Estimation of the probability of death was more precise with APACHE-IICCP (standardized mortality ratio, SMR = 1.03) and SAPS-3 (SMR = 1.08) models. Further analysis showed that discrimination was high with all prognostic model whether for patients with planned ICU admission (AROC APACHE-IICCP 0.97, APACHE-II 0.96, SAPS-3 0.95, SAPS-3CSA 0.95) or for patients with unplanned ICU admission (AROC APACHE-IICCP 0.97, APACHE-II 0.94, SAPS-3 0.86, SAPS-3CSA 0.95). Calibration was good for all predictive models in both subgroups (p value of H–L test > 0.05, except for APACHE-II model inpatients with planned ICU admission). In this prospective study, general predictive models (e.g., APACHE-II, SAPS-3) and cancer-specific models (e.g., APACHE-IICCP) are accurate in predicting hospital mortality. Other studies confirming these results are required.

This study aimed to investigate risk factors associated with oxaliplatin hypersensitivity reactions in cancer patients through a meta-analysis. A comprehensive retrieve of Chinese databases China National Knowledge Infrastructure, Wanfang Data, VIP Database and English databases PubMed, ScienceDirect, Embase and Cochrane library was conducted. The studies that meet the requirements for meta-analysis according to inclusion and exclusion criteria were screened and assessed for eligibility. Odds ratio (OR) / Weighted mean difference (WMD) and 95% confidence intervals (95% CIs) or calculable dichotomous and continuous raw data were extracted to perform meta-analysis using random effect model or fixed effect model on the basis of heterogeneity between studies through Review Manager 5.4 software. A total of 14 cross-sectional studies and 3367 cancer patients were included. Meta-analysis results showed that platinum exposure history (OR value 3.13, 95% CI 2.19–4.48, heterogeneity P = 0.26), allergy history (OR value 1.76, 95% CI 1.09–2.85, heterogeneity P = 0.61), platinum free interval (OR value 3.75, 95% CI 2.00–7.06, heterogeneity P = 0.83), dexamethasone premedication dose (OR value 0.28, 95% CI 0.13–0.58, heterogeneity P = 0.21) were significantly correlated to oxaliplatin hypersensitivity reactions. Gender, age, metastasis, combination with bevacizumab, XELOX regimen and cancer types were detected to have no statistically significant effect on oxaliplatin hypersensitivity reactions. Platinum exposure history, allergy history and long platinum-free interval are risk factors of oxaliplatin hypersensitivity reactions. High dexamethasone premedication dose is a protective factor of oxaliplatin hypersensitivity reactions.

Currently, there is no consensus regarding which patients with high-risk prostate cancer (PCa) would benefit the most by radical prostatectomy (RP). We aimed to identify patients with high-risk PCa who are treatable by RP alone. We retrospectively reviewed data on 315 patients with D’Amico high-risk PCa who were treated using RP without neoadjuvant or adjuvant therapy at the institutions of the Yamaguchi Uro-Oncology Group between 2009 and 2013. The primary endpoint was biochemical progression-free survival (bPFS) after RP. Risk factors for biochemical progression were extracted using the Cox proportional hazard model. We stratified the patients with high-risk PCa into 3 subgroups based on bPFS after RP using the risk factors. At a median follow-up of 49.9 months, biochemical progression was observed in 20.5% of the patients. The 2- and 5-year bPFS after RP were 89.4 and 70.0%, respectively. On multivariate analysis, Gleason score (GS) at biopsy (≥ 8, HR 1.92, p < 0.05) and % positive core (≥ 30%, HR 2.85, p < 0.005) were independent predictors of biochemical progression. Patients were stratified into favorable- (0 risk factor; 117 patients), intermediate- (1 risk factor; 127 patients), and poor- (2 risk factors; 57 patients) risk groups, based on the number of predictive factors. On the Cox proportional hazard model, this risk classification model could significantly predict biochemical progression after RP (favorable-risk, HR 1.0; intermediate-risk, HR 2.26; high-risk, HR 5.03; p < 0.0001). The risk of biochemical progression of high-risk PCa after RP could be stratified by GS at biopsy (≥ 8) and % positive core (≥ 30%).