Multicenter Retrospective Analysis of Original versus Modified FOLFIRINOX in Metastatic Pancreatic Cancer: Results of the NAPOLEON Study.

INTRODUCTION: Original FOLFIRINOX (oFFX) is more toxic than other regimens for patients with metastatic pancreatic cancer (mPC); therefore, a modified FFX (mFFX) regimen with a reduced dosage has been used in Japanese clinical practice. However, very few studies have compared these two regimens. METHODS: This study was conducted as part of a multicenter retrospective study of 318 patients with mPC across 14 centers in Japan (NAPOLEON study). To control for potential bias and confounders, we conducted a propensity score-adjusted analysis of patient characteristics and clinical outcomes. RESULTS: oFFX and mFFX were administered to 48 and 54 patients. More patients with younger age and poorer performance status were included in the oFFX group. The overall survival (OS; median, 11.6 vs. 11.3 months; hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.60-1.40; p = 0.67), progression-free survival (PFS) (median, 6.3 vs. 5.7 months; HR, 0.85; 95% CI, 0.56-1.28; p = 0.44), and overall response rate (29 vs. 26%, p = 0.71) were not significantly different for the oFFX and mFFX groups. Thrombopenia and liver dysfunction were significantly more frequent with oFFX than with mFFX. The median received dose intensity of CPT-11 was higher with oFFX than with mFFX (299 vs. 270 mg/m2/week, p < 0.01). The propensity score-adjusted analysis revealed no statistically significant differences in OS and PFS between the two groups. CONCLUSION: In our data, there was no significant difference in efficacy between mFFX and oFFX, and mFFX has fewer adverse events.

Scoring model with serum albumin and CA19-9 for metastatic pancreatic cancer in second-line treatment: results from the NAPOLEON study.

BACKGROUND: Patients with metastatic pancreatic cancer refractory to first-line chemotherapy (CTx) have few treatment options. It is unclear what kind of patients could be brought about survival benefit by 2nd-line CTx after refractory to gemcitabine + nab-PTX (GnP) or FOLFIRINOX. METHODS: This analysis was conducted as part of a multicenter retrospective study of GnP or FOLFIRINOX in patients with metastatic pancreatic cancer. Excluding censored cases, 156 and 77 patients, respectively, received second-line chemotherapy (CTx) and best supportive care (BSC). Using prognostic factors for post-discontinuation survivals (PDSs) at the first-line determination in multivariate analysis, we developed a scoring system to demonstrate the benefit of second-line CTx. RESULTS: The second-line CTx group had a median PDS of 5.2 months, whereas the BSC group had a median PDS of 2.7 months (hazard ratio 0.42; 95% confidence interval [CI] 0.31-0.57; p < 0.01). According to the Cox regression model, serum albumin levels below 3.5 g/dL, and CA19-9 levels above 1000 U/mL were independent prognostic factors (p < 0.01). Serum albumin (≥ and < 3.5 g/dL allotted to scores 0 and 1) and CA19-9 (< and ≥ 1000 U/mL allotted to scores 0 and 1) at first-line determination were used to develop the scoring system. The PDSs of patients with scores of 0 and 1 were significantly better than those of the BSC group; however, there was no significant difference between the PDSs of patients with score 2 and the BSC group. CONCLUSION: The survival advantage of second-line CTx, was observed in patients with scores of 0 and 1 but not in those with score 2.

Prognostic nomogram for patients with unresectable pancreatic cancer treated with gemcitabine plus nab-paclitaxel or FOLFIRINOX: A post-hoc analysis of a multicenter retrospective study in Japan (NAPOLEON study).

BACKGROUND: No reliable nomogram has been developed until date for predicting the survival in patients with unresectable pancreatic cancer undergoing treatment with gemcitabine plus nab-paclitaxel (GnP) or FOLFIRINOX. METHODS: This analysis was conducted using clinical data of Japanese patients with unresectable pancreatic cancer undergoing GnP or FOLFIRINOX treatment obtained from a multicenter study (NAPOLEON study). A Cox proportional hazards model was used to identify the independent prognostic factors. A nomogram to predict 6-, 12-, and 18-month survival probabilities was generated, validated by using the concordance index (C-index), and calibrated by the bootstrapping method. And then, we attempted risk stratification for survival by classifying the patients according to the sum of the scores on the nomogram (total nomogram points). RESULTS: A total of 318 patients were enrolled. A prognostic nomogram was generated using data on the Eastern Cooperative Oncology Group performance status, liver metastasis, serum LDH, serum CRP, and serum CA19-9. The C-indexes of the nomogram were 0.77, 0.72 and 0.70 for 6-, 12-, and 18-month survival, respectively. The calibration plot showed optimal agreement at all points. Risk stratification based on tertiles of the total nomogram points yielded clear separations of the survival curves. The median survival times in the low-, moderate-, and high-risk groups were 15.8, 12.8 and 7.8 months (P<0.05), respectively. CONCLUSIONS: Our nomogram might be a convenient and inexpensive tool to accurately predict survival in Japanese patients with unresectable pancreatic cancer undergoing treatment with GnP or FOLFIRINOX, and will help clinicians in selecting appropriate therapeutic strategies for individualized management.

A multicentre retrospective study comparing site-specific treatment with empiric treatment for unfavourable subset of cancer of unknown primary site.

BACKGROUND: Patients with cancer of unknown primary site are divided into two distinct groups, favourable and unfavourable subsets. For the unfavourable subset, empiric treatment or site-specific treatment is recommended, but limited knowledge exists about the efficacy of site-specific treatment compared with empiric treatment in clinical practice. METHODS: In this multicentre retrospective study, we reviewed the medical records of patients with cancer of unknown primary site treated with chemotherapy (or chemoradiotherapy) as first-line treatment from eight institutions during 2006-18. We investigated the workup modality and categorized the patients into favourable and unfavourable subsets, which were further divided into site-specific and empiric treatment groups. Site-specific treatment is defined as a standard chemotherapy for an estimated primary site. We examined the efficacy in the favourable and unfavourable subsets and performed multivariable analysis for estimating the overall survival in the unfavourable subset. RESULTS: Of 177 patients with cancer of unknown primary site, 33 and 144 were categorized into favourable and unfavourable subsets, respectively. In the unfavourable subset, 84 patients (58.3%) received empiric therapy, and 60 patients (41.7%) received site-specific treatment. Median overall survival was 10.0 and 10.1 months in site-specific and empiric treatment groups, respectively, with no significant difference (hazard ratio 1.01, 95% confidence interval 0.70-1.45, P = 0.95). Multivariable analysis revealed performance status, number of metastatic sites and hypoalbuminaemia as independent prognostic factors for overall survival in the unfavourable subset. CONCLUSIONS: Overall survival in site-specific and empiric treatment groups was similar in the unfavourable cancer of unknown primary site subset in this study. Further research is needed to prolong overall survival in patients in the unfavourable cancer of unknown primary site subset.

A multicenter propensity score analysis of FOLFIRINOX vs gemcitabine plus nab-paclitaxel administered to patients with metastatic pancreatic cancer: results from the NAPOLEON study.

PURPOSE: Fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX, FFX) and gemcitabine plus nab-paclitaxel (GnP) are considered standard treatments for patients with metastatic pancreatic cancer. Direct comparisons are not available that establish which is optimal. METHODS: We conducted a propensity score-adjusted analysis of patients with metastatic pancreatic cancer to identify the therapeutic advantages of these standard therapies. We used clinical data as part of a multicenter retrospective study of patients with unresectable or recurrent pancreatic cancer treated with FFX or GnP (NAPOLEON study). RESULTS: FFX and GnP were initially administered to 102 and 153 patients, respectively. The GnP group comprised more patients of advanced age, worse performance status, lower body mass index, recurrence, and lower albumin concentrations. Median overall survival (OS) and progression-free survival (PFS) were 11.5 months and 5.8 months in the FFX group and 11.1 months and 5.9 months in the GnP group, respectively. Propensity score-adjusted analysis indicated that the administration of FFX or GnP was not independently associated with OS (adjusted hazard ratio [HR] 1.06; 95% confidence interval [CI] 0.76-1.47; P = 0.73). Similarly, the difference in PFS was not significant between groups (adjusted HR 0.93; 95% CI 0.68-1.26; P = 0.62). Gastrointestinal disorders were more common in the FFX group, whereas the frequencies of hematological, nervous system, and skin disorders were higher in the GnP group. CONCLUSION: The efficacies of FFX and GnP were comparable, although safety profiles differed and should be considered in selecting treatment.

Phase I Study of Alternate-Day Administration of S-1, Oral Leucovorin, and Bevacizumab for Refractory Metastatic Colorectal Cancer.

LESSONS LEARNED: The recommended S-1 dose was 40 mg/m2 , twice daily on Monday, Wednesday, Friday, and Sunday, with oral leucovorin and bevacizumab. Compared with daily administration, the alternate-day administration of S-1 with oral leucovorin may reduce mucositis with promising antitumor activity in refractory metastatic colorectal cancer. BACKGROUND: Daily S-1 plus oral leucovorin administration in a 1-week-on/1-week-off schedule has promising efficacy in gastrointestinal cancer but is associated with high risk of mucositis and diarrhea. METHODS: This phase Ib, 3+3 dose-escalation trial included patients with chemorefractory metastatic colorectal cancer (mCRC) receiving S-1 (40 mg/m2 ) and leucovorin (25 mg) orally twice daily (level 1, even-numbered days; level 2, Monday, Wednesday, Friday, and Sunday) and intravenous bevacizumab (5 mg/kg) every 2 weeks. Enrollment continued at the recommended dose level in the expansion cohort. RESULTS: We enrolled 21 patients (3 and 18 patients in levels 1 and 2, respectively). Briefly, 12 and 9 patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0 and 1, respectively, and 8 and 13 patients had 1-3 and ≥4 prior treatment lines, respectively. Dose-limiting toxicity (DLT) was not observed, and level 2 was confirmed as the recommended dose. Common grade 3-4 adverse events at level 2 were anemia (22%), anorexia (6%), and diarrhea (6%). In the entire cohort, response rate, disease control rate, and median progression-free survival were 10%, 71%, and 4.2 months, respectively. CONCLUSION: The recommended S-1 dose was 40 mg/m2 , twice daily on Monday, Wednesday, Friday, and Sunday, with 25 mg oral leucovorin twice daily and 5 mg/kg bevacizumab every 2 weeks. Compared with the daily administration, alternate-day administration of S-1 plus leucovorin may reduce mucositis with promising antitumor activity in refractory mCRC.

The association of primary tumor site with acute adverse event and efficacy of definitive chemoradiotherapy for cStage II/III esophageal cancer: an exploratory analysis of JCOG0909.

BACKGROUND: JCOG0909 is a phase II trial of definitive chemoradiotherapy including salvage treatment for cStage II-III thoracic esophageal cancer; the radiation field for elective regional lymph node irradiation, which can affect patient outcome and adverse event, varied based on the primary tumor site, i.e., upper (Ut), middle (Mt), and lower thoracic (Lt) esophagus. The impact of different primary sites on the safety and efficacy of definitive chemoradiotherapy in JCOG0909 is not well characterized. METHODS: Patients were categorized into three groups (Ut, Mt, and Lt) according to the primary tumor location. We compared acute adverse events during definitive chemoradiotherapy, complete response (CR) rate, 3-year progression-free survival (PFS), and overall survival (OS) among the 3 groups. RESULTS: Out of the 96 patients enrolled in JCOG0909 between April 2010 and August 2014, 94 patients (16, 59, and 19 patients in the Ut, Mt, and Lt groups, respectively) were included in this exploratory analysis. The proportion of patients with cStage III was 25% in the Ut, 37% in the Mt, and 47% in the Lt group. Grade 3-4 leukopenia, neutropenia, and thrombocytopenia were more frequently observed in the Mt (66%, 54%, and 15%) and Lt groups (84%, 68%, and 16%) than in the Ut group (38%, 44%, and 0%). There was no significant between-group difference with respect to 3-year OS (73.3%, 77.9%, and 57.9%), 3-year PFS (60.0%, 59.3%, and 47.4%), or CR rate (62.5%, 62.7%, and 42.1%). CONCLUSIONS: In JCOG0909, the incidence of severe hematological toxicity had a trend toward higher in the Mt and Lt than the Ut esophageal cancer; however, no remarkable difference by primary sites was observed with respect to efficacy endpoints.

Salvage chemotherapy with the combination of oxaliplatin, leucovorin, and 5-fluorouracil in advanced gastric cancer refractory or intolerant to fluoropyrimidines, platinum, taxanes, and irinotecan.

BACKGROUND: Although nivolumab showed survival benefit in patients with advanced gastric cancer (AGC) progressing after standard chemotherapy, there is a lack of data regarding oxaliplatin-based chemotherapy in this clinical setting. METHODS: We retrospectively evaluated the efficacy and safety of oxaliplatin with l-leucovorin and bolus/continuous infusion of 5-fluorouracil as salvage treatment in patients with AGC refractory or intolerant to fluoropyrimidines, cisplatin, taxanes, and irinotecan. RESULTS: Overall, 50 patients treated between December 2009 and December 2013 were included in this analysis. The overall response rate (ORR) was 21.2% among 33 patients with measurable disease. The median time to treatment failure (TTF) and overall survival (OS) were 2.4 and 4.2 months. In multivariate analysis, factors associated with OS included poor performance status [hazard ratio (HR) 3.20; 95% confidence interval (CI) 1.55-6.60], shorter time from the start of first-line therapy (HR 2.20; 95% CI 1.18-4.12), and higher neutrophil/lymphocyte ratio value (HR 4.87; 95% CI 2.32-10.25). In patients (n = 35) with at most one risk factor, the ORR, median TTF, and OS were 26.1%, 3.6, and 6.7 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (30%), anemia (22%), febrile neutropenia (8%), and peripheral neuropathy (8%). Initial and subsequent dose reduction was performed in 18 (36%) and 23 (46%) patients. There was one treatment-related death caused by septic infection. CONCLUSIONS: Salvage chemotherapy with the combination of oxaliplatin, leucovorin, and 5-fluorouracil has a potential activity and is tolerable for heavily treated AGC with appropriate dose modification and patient selection.

Efficacy of Second-Line Bevacizumab-Containing Chemotherapy for Patients with Metastatic Colorectal Cancer following First-Line Treatment with an Anti-Epidermal Growth Factor Receptor Antibody.

OBJECTIVE: Anti-epidermal growth factor receptor (EGFR) antibodies and bevacizumab are commonly used, sequentially, as palliative chemotherapies for patients with metastatic colorectal cancer. However, little is known about the efficacy of second-line treatments containing bevacizumab after first-line treatment with an anti-EGFR antibody. METHODS: We retrospectively reviewed 128 patients who received second-line bevacizumab-containing chemotherapy and evaluated the effect of prior use of anti-EGFR antibody on the efficacy of the second-line treatment. RESULTS: As first-line treatments, 35 of these patients received only cytotoxic chemotherapy (cohort A), 58 received bevacizumab-containing chemotherapy (cohort B), and 35 received anti-EGFR-containing chemotherapy (cohort C). The median progression-free survival (PFS) with the second-line bevacizumab-containing therapy was 8.3 months in cohort C, 6.9 months in cohort A (hazard ratio [HR], 1.43; 95% confidence interval [CI], 0.83-2.51), and 5.6 months in cohort B (HR, 1.95; 95% CI, 1.18-3.22). Multivariate analysis showed that PFS in cohort C was the same as that in cohort A, but better than that in cohort B. The overall response rate in cohort C (25.7%) was also similar to that in cohort A (20.0%), but better than that in cohort B (10.3%). CONCLUSIONS: Prior use of anti-EGFR antibody did not adversely affect the efficacy of subsequent bevacizumab-containing chemotherapy.

Serum CA19-9 Response Is an Early Predictive Marker of Efficacy of Regorafenib in Refractory Metastatic Colorectal Cancer.

PURPOSE: Regorafenib improves survival in chemorefractory metastatic colorectal cancer (mCRC) patients. However, regorafenib induces various adverse events (AEs) that often impair patients' quality of life. Identification of early predictive markers of the efficacy is warranted. METHODS: We retrospectively examined 146 consecutive mCRC patients who received regorafenib. Clinical parameters, including patient background, AEs, and changes in biochemical parameters until day 28, were evaluated to identify efficacy predictors. RESULTS: Median progression-free survival (PFS) was 2.1 months, and median overall survival was 6.6 months. Major AEs in all cycles were hand-foot skin reaction, hypertension, and increased aspartate transaminase. We extracted 121 patients for prognostic analysis. In univariate analysis, decreased carcinoembryonic antigen (HR: 0.570, p = 0.012) and decreased carbohydrate antigen 19-9 (CA19-9) (HR: 0.422, p = 0.0012) were identified as prognostic markers of PFS. Patients in whom serum CA19-9 decreased after regorafenib exhibited significantly better PFS (median 3.7 vs. 2.0 months, p = 0.004) than those in whom serum CA19-9 did not decrease. Multivariate analysis revealed early CA19-9 decrease as an independent predictive factor (HR: 0.415, 95% CI: 0.210-0.818, p = 0.011). CONCLUSION: Early response of CA19-9 may predict the efficacy of regorafenib. Additional studies are needed for external validation.

Association between ABCG2 and SLCO1B1 polymorphisms and adverse drug reactions to regorafenib: a preliminary study
.

OBJECTIVE: Due to the occurrence of severe adverse drug reactions to regorafenib, a drug used in cancer therapy, the identification of a predictive marker(s) is needed to increase the therapeutic applicability of this compound. We therefore investigated whether polymorphisms in the ABCG2 and SLCO1B genes are associated with adverse drug reactions to regorafenib. METHODS: For these analyses, 37 Japanese cancer patients were treated with regorafenib, genotyped for polymorphisms in ABCG2 and SLCO1B, and evaluated for drug-related adverse drug reactions. RESULTS: There was no association between the ABCG2 421C>A variant and adverse drug reactions to regorafenib. After treatment, the incidences of increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as increased total bilirubin (grade ≥ 2) were 8%, 4%, and 12%, and 42%, 25%, and 25% among SLCO1B1*1b carriers and non-carriers, respectively. There were no significant associations between elevated ALT and bilirubin and the SLCO1B1*1b allele. However, there were significantly lower incidences of increased AST (8% vs. 42%) and anemia (16% vs. 50%) in SLCO1B1*1b carriers than in non-carriers. CONCLUSIONS: The absence of SLCO1B1*1b allele appears to be associated with the development of adverse drug reactions to regorafenib; however, further studies involving larger test groups and other populations are needed to confirm these findings.
.

A short interval between bevacizumab and anti-epithelial growth factor receptor therapy interferes with efficacy of subsequent anti-EGFR therapy for refractory colorectal cancer.

BACKGROUND: Both bevacizumab and anti-epithelial growth factor receptor (EGFR) agents (e.g. cetuximab and panitumumab) are sequentially used for metastatic colorectal cancer (mCRC). Their co-administration as a first-line treatment does not improve outcome, indicating that there are negative interactions between these agents. A long-term pharmacokinetics study demonstrated serum persistence of bevacizumab following termination of bevacizumab 6 months after the last administration. This prompted us to investigate the impact of short intervals between bevacizumab and anti-EGFR antibody on the efficacy of subsequent anti-EGFR therapy. METHODS: We retrospectively reviewed consecutive patients with KRAS exon 2 wild-type mCRC who underwent anti-EGFR therapy after the failure of fluoropyrimidines, oxaliplatin and irinotecan. We divided patients into two groups (Group A: the interval between bevacizumab and anti-EGFR agent< 6 months; Group B: the interval >6 months). RESULTS: Of the 114 included patients (median age, 63 years), 78 (68%) were male. Most patients (88%) were treated with cetuximab plus irinotecan. Groups A and B consisted of 74 and 40 patients, respectively. There were no significant differences in patient characteristics. Group B patients had significantly longer progression-free survival (4.2 vs. 6.6 months; HR, 0.65; 95% CI, 0.43-0.98; P = 0.038) and longer overall survival (11.6 vs. 14.3 months; HR, 0.63; 95% CI, 0.41-0.98, P = 0.039). The response rate was 24.3% in Group A and 47.5% in Group B (P = 0.012). CONCLUSION: A short interval between bevacizumab and anti-EGFR antibody treatment may interfere with the efficacy of subsequent anti-EGFR therapy.

Comparison between surgery and definitive chemoradiotherapy for patients with resectable esophageal squamous cell carcinoma: a propensity score analysis.

PURPOSE: Our intent was to compare survival following neoadjuvant chemotherapy followed by surgery versus chemoradiotherapy (CRT) among patients with potentially resectable esophageal squamous cell carcinoma. METHODS: Information about 406 consecutive esophageal cancer patients with resectable disease who underwent surgery with neoadjuvant chemotherapy consisting of cisplatin plus 5-fluorouracil or who underwent definitive CRT was reviewed. The survival outcomes were analyzed using the Kaplan-Meier method and propensity score-adjusted Cox proportional hazards models. Relevant variables were included in the propensity score model. RESULTS: Overall, 206 patients planned to undergo surgery (S group) and 200 patients planned to undergo CRT (CRT group). In the unadjusted situation, progression-free survival and overall survival did not differ statistically between the groups. After matching, both survival outcomes were better in the S group compared to the CRT group. Subanalysis showed both survival outcomes were better in the S group for patients with only stage III disease. However, survival outcomes for stages I, II, and IV were not significantly different between treatment groups. CONCLUSIONS: Among patients with resectable disease, survival outcomes in the S group were favored over those of the CRT group. These results indicate that different therapeutic strategies should be used for stage III esophageal cancer than for other stages.

A single-arm phase II trial of combined chemotherapy with S-1, oral leucovorin, and bevacizumab in heavily pre-treated patients with metastatic colorectal cancer.

BACKGROUND: The mean 5-6-month survival after failed standard chemotherapy for metastatic colorectal cancer (mCRC) necessitates more effective treatments for refractory mCRC. For untreated mCRC, S-1 + oral leucovorin (SL) therapy offers promising results without severe toxicity. The ML18147 trial demonstrated that bevacizumab (Bev) prolongs overall survival after mCRC progression. We conducted a single-centre phase-II trial to evaluate the safety and efficacy of SL/Bev combination chemotherapy as mCRC salvage therapy. METHODS: Major eligibility criteria were confirmed adenocarcinoma diagnosis; age >20 years; Eastern Cooperative Oncology Group performance status, 0-2; and progression after administration/intolerance of/to approved drugs for mCRC. (5-FU, oxaliplatin, irinotecan, Bev, and anti-EGFR antibody, if KRAS wild-type). S-1 (80-120 mg/body) and leucovorin (25 mg) were orally administered in a 1-week-on/1-week-off schedule. Bev (5 mg/kg) was administered on day 1 of every 2-week cycle. The primary endpoint was disease control rate (DCR). RESULTS: A total of 31 patients were enrolled. DCR was 65% [95% confidence interval (CI), 48-100%] and the response rate was 7% (95% CI, 0.7-22%). One patient showing partial response to SL/Bev had a BRAF-mutant tumor. Median progression-free survival and overall survivals were 5.3 [95% CI, 2.1-9.3] and 9.9 [95% CI, 7.4-NA] months, respectively. The most-frequent grade-3/4 adverse events were mucositis (26%) and diarrhea (11%), which were manageable by dose reduction/interruption. CONCLUSIONS: SL/Bev showed impressive activity in refractory mCRC and was tolerable, suggesting its potential as an alternative chemotherapy for refractory mCRC. TRIAL REGISTRATION: This study has been registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( ID UMIN000009083 ) on 11 October 2012.

Differences in attitude toward adjuvant chemotherapy between colorectal cancer survivors and the medical staff of Japanese hospitals.

BACKGROUND: Adding oxaliplatin to fluorouracil-based chemotherapy can improve the survival of patients with stage III colorectal cancer by approximately 20 %. Reportedly, cancer patients are much more likely to prefer chemotherapy than medical professionals, although there is only a very small chance of achieving benefits from treatment. However, chronic neurotoxicity may be long lasting after the administration of oxaliplatin-based chemotherapy. This study aimed to evaluate potential side effects and differences in attitude between colorectal cancer patients and medical staff regarding the risk-benefit trade-offs of chemotherapy. METHODS: Relapse-free colorectal cancer patients who received adjuvant chemotherapy, doctors, and nurses were surveyed using a questionnaire regarding the side effects of chemotherapy and hypothetical clinical scenarios to quantify gains in the risk of relapse that were deemed necessary to make chemotherapy worthwhile. RESULTS: Responses were obtained from 147 patients, 54 doctors, and 84 nurses. Of these, 39 % of patients and 85 % of doctors replied that moderate side effects of adjuvant chemotherapy were worthwhile to achieve an absolute gain in the risk of relapse of 10 % from a baseline of 40 %. More severe side effects, as reported by colorectal cancer patients, were not associated with the larger gains necessary to make treatment worthwhile. Seven percent of patients treated with oxaliplatin, 40 % of doctors, and 43 % of nurses replied that side effects associated with oxaliplatin-based chemotherapy were severe. CONCLUSIONS: Doctors should consider potential heterogeneity in side effects and attitudes regarding the risk-benefit balance of adjuvant chemotherapy, and that patient perspectives should enhance shared decision-making.

[A questionnaire survey on QOL and toxicity in colorectal cancer survivors who received adjuvant chemotherapy].

The relative risk of cancer recurrence with postoperative adjuvant FOLFOX/CapeOX therapy(Ox)for stage III colorectal cancer is reduced by approximately 20%when compared to that with fluorouracil plus Leucovorin. We performed a questionnaire survey to evaluate the quality of life(QOL)and extent of side effects in patients who received adjuvant chemotherapy. In order to evaluate the risks and benefits of oxaliplatin administration, we also examined the differences in awareness of oxaliplatin side effects between patients and medical staff. Responses were obtained from 147 patients, 54 doctors, and 84 nurses. Analysis of the patient responses showed higher current QOL scores regardless of the chemotherapy regimen, although patients in the Ox group had a high rate of residual sensory peripheral neuropathy. In the Ox group, 81% of patients responded that the side effects were moderate. In contrast, 40% of medical staff identified the side effects of oxaliplatin as severe, which differed from that reported by the patients. Considering that Ox adjuvant chemotherapy may reduce the risk of recurrence by approximately 20%, the risk/benefit balance is acceptable.

Long-term outcomes and prognostic factors of patients with advanced gastric cancer treated with S-1 plus cisplatin combination chemotherapy as a first-line treatment.

BACKGROUND: The long-term outcomes of advanced gastric cancer (AGC) patients treated with S-1 plus cisplatin (SP) combination chemotherapy remain unclear. Therefore, we sought to evaluate these outcomes to identify the prognostic factors affecting patient survival. METHODS: We retrospectively analyzed 153 AGC patients treated with SP at a single institution between January 2005 and July 2011. RESULTS: Median overall survival (OS) was 15.0 months [95 % confidence interval (CI), 12.5-17.9 months]. Three independent prognostic factors affecting poor survival were identified: performance status (PS) ≥ 1 [hazard ratio (HR) = 2.39, 95 % CI, 1.58-3.62); >1 metastatic site (HR = 1.57, 95 % CI, 1.10-2.26], and elevated alkaline phosphatase levels (HR = 1.70, 95 % CI, 1.16-2.49). A simple prognostic index was generated using three risk groups: good (no risk factor), moderate (one or two risk factors), and poor (three risk factors). The median OS for good-, moderate-, and poor-risk groups was 28.6, 14.8, and 7.3 months, respectively (log-rank test; P < 0.0001). Among the twelve 3-year survivors, 9 (75 %) had a PS of 0 and 8 (67 %) had only one metastatic site. CONCLUSIONS: Three prognostic factors were identified in AGC patients treated with SP. Using a simple prognostic index, the patients were divided into three risk groups, in which the survival differences were markedly significant, suggesting that patients with good PS and only one metastatic site may have a higher chance of long-term survival than those with poor PS and multiple metastatic sites.

A multicenter retrospective observational NAPOLEON2 study of nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable pancreatic cancer.

Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer. However, there are limited clinical data on its efficacy and safety in the real-world. We therefore initiated a retrospective and prospective observational study (NAPOLEON-2). The results of the retrospective part were reported herein. In this retrospective study, we evaluated 161 consecutive patients who received NFF as second-or-later-line regimen. The main endpoint was overall survival (OS), and the other endpoints were response rate, disease control rate, progression-free survival (PFS), dose intensity, and adverse events (AEs). The median age was 67 years (range, 38-85 years). The median OS and PFS were 8.1 and 3.4 months, respectively. The objective response and disease control rates were 5% and 52%, respectively. The median relative dose intensity was 81.6% for nanoliposomal irinotecan and 82.9% for fluorouracil. Grade 3 or 4 hematological and nonhematological AEs occurred in 47 and 42 patients, respectively. Common grade 3 or 4 AEs included neutropenia (24%), anorexia (12%), and leukocytopenia (12%). Subanalysis of patients treated with second-line and third-or-later-line demonstrated no statistical significant difference in OS (7.6 months vs. 9.1 months, respectively; hazard ratio, 0.92; 95% confidence interval, 0.64-1.35; p = 0.68). In conclusion, NFF has acceptable efficacy and safety profile even in real-world clinical settings. The prospective study is in progress to validate these findings.

Real-World Treatment Sequencing in Vulnerable Patients with Metastatic Colorectal Cancer: A Multicenter Retrospective Study.

BACKGROUND: Data regarding treatment sequence for vulnerable patients with metastatic colorectal cancer (mCRC) in a real-world setting are lacking. OBJECTIVE: We aimed to assess treatment outcomes in second-line or later chemotherapy for vulnerable patients with mCRC in a real-world setting. PATIENTS AND METHODS: Vulnerable patients with mCRC who received less intensive treatment ('vulnerable') regimens, i.e. fluoropyrimidines with or without biologics (FP), reduced-dose doublet regimens with or without biologics (Doublet), and anti-epidermal growth factor receptor monotherapy (Anti-EGFR), as first-line therapy between June 2015 and December 2018 were retrospectively reviewed. RESULTS: A total of 210 patients from 15 hospitals were analyzed. The median age was 78 years (range 28-90), and 44 patients (21%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 2. In the entire population, the median time to treatment failure (TTF) and overall survival (OS) were 7.6 and 21.4 months, respectively. Following the failure of first-line therapy in 195 patients, 74 (38%), 24 (12%), and 13 (7%) patients received vulnerable regimens, full-dose doublet regimens with or without biologics, and other regimens, respectively, whereas 84 (43%) received best supportive care (BSC). In patients receiving vulnerable regimens as second-line therapy, the median TTF and OS were 4.4 and 13.7 months, respectively, while response rate and disease control rate were 18% and 62%, respectively. In 84 patients who received BSC, the median OS was 3.5 months. CONCLUSIONS: Second-line chemotherapy for vulnerable patients with mCRC showed clinically meaningful outcomes; however, few patients received second-line therapy, and survival among patients who received BSC was dismal.