Completion Rate Of Chemotherapy Research Articles

Hepatectomy followed by adjuvant chemotherapy with capecitabine plus oxaliplatin for three months for colorectal cancer liver metastases: A multicenter phase 2 study.

e15015 Background: Hepatic resection is one of the treatment strategies for resectable colorectal cancer liver metastases (CLM). The role of neoadjuvant and adjuvant chemotherapy in the management of initially resectable CLM is still unclear. Adjuvant chemotherapy consisting of capecitabine plus oxaliplatin (CapeOx) appears to be equivalent to FOLFOX in patients with stage III colon cancer. Furthermore, some studies suggest that adjuvant chemotherapy for three months after curative resection for stage II/III colorectal cancer has equivalent efficacy to adjuvant chemotherapy for 6 months. We initiated a multi-institutional, single-arm, open label, phase II trial to confirm the feasibility of adjuvant CapeOx for three months for post curative resection of CLM. Methods: Patients received one course of capecitabine followed by four courses of CapeOx for a total five courses (15 weeks) as adjuvant chemotherapy after curative resection of CLM. CapeOx consisted of a 2-hour intravenous infusion of oxaliplatin 130 mg/m2 on day 1 plus oral capecitabine 1,000 mg/m2 twice daily for 2 weeks in a 3-week cycle. The primary endpoint was completion rate of adjuvant chemotherapy. We set a threshold completion rate of protocol treatment of 45% and an expected completion rate of 70%. Given a one-sided α of 0.1 and statistical power of 80%, a minimum of 25 patients was required. Results: From May 2013 to November 2015, Twenty-eight patients were enrolled from six institutions: median age 69.5y, 54% male, 78.5% left-sided primary. Of the patients, 15 were synchronous metastases and 13 were metachronous. The locations of the metastases were unilobar in 20 patients and bilobar in 8. The mean number of lesions resected was two (range, 1 to 4). The mean size of largest tumor was 31 mm (range, 2 to 112 mm). Among the 28 patients, 20 (71.4 %: 95% CI, 53.6 to 89.3%) completed the protocol treatment. The most common grade 3 or 4 toxicities were neutropenia (29%). No treatment related death was observed. Conclusions: Adjuvant CapeOx for three months for post curative resection of CLM was feasible. Clinical trial information: UMIN000011164.

The basal nutritional state of PDAC patients is the dominant factor for completing adjuvant chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and several clinical trials have shown that adjuvant chemotherapy after curative resection can improve the prognosis of these patients. However, the adjuvant chemotherapy completion rate is less than satisfactory. If this rate could be increased then the overall prognosis of PDAC might be improved; however, reports addressing this problem are insufficient. To elucidate the factors, we retrospectively investigated PDAC patients. Various factors of 121 PDAC patients undergoing R0 resection, including preoperatively treated patients, were investigated. Univariate and multivariate analyses were performed to investigate the factors that were associated with the completion of adjuvant chemotherapy. The analysis identified age and the prognostic nutritional index (PNI) as significant independent factors. A receiver operating characteristic curve analysis of age yielded a cutoff value of 67 years (sensitivity, 64%; specificity, 78%). Univariate and multivariate analyses of the 61 patients who were over 67 years of age revealed that the PNI (odds ratio, 0.85; P = 0.048) and Evans grade (odds ratio, 0.041; P = 0.0010) were significant factors for the completion of chemotherapy. The results of our investigation suggest that nutrition should be controlled in older PDAC patients to facilitate the completion of adjuvant chemotherapy.

Perioperative Epirubicin, Oxaliplatin, and Capecitabine Chemotherapy in Locally Advanced Gastric Cancer: Safety and Feasibility in an Interim Survival Analysis.

PurposePerioperative chemotherapy improves survival outcomes in locally advanced (LA) gastric cancer.Materials and MethodsWe retrospectively analyzed patients with LA gastric cancer who were offered perioperative chemotherapy consisting of epirubicin, oxaliplatin, and capecitabine (EOX) from May 2013 to December 2015 at Tata Memorial Hospital in Mumbai.ResultsAmong the 268 consecutive patients in our study, 260 patients (97.0%) completed neoadjuvant chemotherapy, 200 patients (74.6%) underwent D2 lymphadenectomy, and 178 patients (66.4%) completed adjuvant chemotherapy. The median follow-up period was 17 months. For the entire cohort, the median overall survival (OS), 3-year OS rate, median progression-free survival (PFS), and 3-year PFS rate were 37 months, 64.4%, 31 months, and 40%, respectively. PFS and OS were significantly inferior in patients who presented with features of obstruction than in those who did not (P=0.0001). There was no difference in survival with respect to tumor histology (well to moderately differentiated vs. poorly differentiated, signet ring vs. non-signet ring histology) or location (proximal vs. distal). Survival was prolonged in patients with an early pathological T stage and a pathological node-negative status. In a multivariate analysis, postoperative pathological nodal status and gastric outlet obstruction on presentation significantly correlated with survival.ConclusionsEOX chemotherapy with curative resection and D2 lymphadenectomy is a suggested alternative to the existing perioperative regimens. The acceptable postoperative complication rate and relatively high resection, chemotherapy completion, and survival rates obtained in this study require further evaluation and validation in a clinical trial.

Preoperative chemoradiotherapy does not compromise the feasibility of adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma.

Preoperative chemoradiotherapy (CRT) is a novel, emerging treatment strategy for pancreatic ductal adenocarcinoma (PDAC), but it remains unclear whether post-surgery adjuvant chemotherapy is feasible following preoperative CRT. This retrospective study evaluates the feasibility of adjuvant therapy after preoperative CRT. The subjects of this study were 99 consecutive patients who underwent pancreatectomy for PDAC between January, 2007 and February, 2013 in our hospital. Sixty patients received preoperative CRT: as gemcitabine (GEM) and 40Gy radiation in 28 (G-CRT group), and as GEM, S-1, and 50.4Gy radiation in 32 (GS-CRT group). We also evaluated 39 patients who underwent surgery alone (SA group). We investigated adjuvant chemotherapy induction and completion rates and the frequency of adverse events rated ≥grade 3, based on Common Terminology Criteria for Adverse Events (version 4.0) in all three groups. In the G-CRT, GS-CRT, and SA groups, the induction rates were 78% (22/28), 78% (25/32), and 72% (28/39), respectively; completion rates were 86% (19/22), 88% (22/25), and 82% (23/28), respectively; and adverse event frequencies were 36% (8/22), 28% (7/25), and 43% (12/28), respectively. No significant difference was found among the three groups. Preoperative CRT was demonstrated to be safe and did not compromise the feasibility of adjuvant chemotherapy.

Comorbidity and outcomes of concurrent chemo- and radiotherapy in limited disease small cell lung cancer

Background: Many patients with limited disease small cell lung cancer (LD SCLC) suffer from comorbidity. Not all patients with comorbidity are offered standard treatment, though there is little evidence for such a policy. The aim of this study was to investigate whether patients with comorbidity had inferior outcomes in a LD SCLC cohort.Material and methods: We analyzed patients from a randomized study comparing two three-week schedules of thoracic radiotherapy (TRT) plus standard chemotherapy in LD SCLC. Patients were to receive four courses of cisplatin/etoposide and TRT of 45 Gy/30 fractions (twice daily) or 42 Gy/15 fractions (once daily). Responders received prophylactic cranial irradiation (PCI). Comorbidity was assessed using the Charlson Comorbidity Index (CCI), which rates conditions with increased one-year mortality.Results: In total 157 patients were enrolled between May 2005 and January 2011. Median age was 63 years, 52% were men, 16% had performance status 2, and 72% stage III disease. Forty percent had no comorbidity; 34% had CCI-score 1; 15% CCI 2; and 11% CCI 3–5. There were no significant differences in completion rates of chemotherapy, TRT or PCI across CCI-scores; or any significant differences in the frequency of grade 3–5 toxicity (p = 0.49), treatment-related deaths (p = 0.36), response rates (p = 0.20), progression-free survival (p = 0.18) or overall survival (p = 0.09) between the CCI categories.Conclusion: Patients with comorbidity completed and tolerated chemo-radiotherapy as well as other patients. There were no significant differences in response rates, progression-free survival or overall survival – suggesting that comorbidity alone is not a reason to withhold standard therapy in LD SCLC.

Effects of an Exercise Program in Colon Cancer Patients undergoing Chemotherapy

Fatigue is a common problem among colon cancer patients and typically increases during chemotherapy. Exercise during chemotherapy might have beneficial effects on fatigue. To investigate the short- and long-term effects of an exercise program in colon cancer patients during adjuvant treatment, the Physical Activity During Cancer Treatment study was conducted. In this multicenter randomized controlled trial, 33 colon cancer patients undergoing chemotherapy (21 men and 12 women) were randomly assigned to either a group receiving an 18-wk supervised exercise program (n = 17) or to usual care (n = 16). The primary outcome was fatigue as measured by the Multidimensional Fatigue Inventory and the Fatigue Quality List. Secondary outcomes were quality of life, physical fitness, anxiety, depression, body weight, and chemotherapy completion rate. Outcome assessment took place at baseline, postintervention (18 wk) and at 36 wk. Intention-to-treat mixed linear model analyses showed that patients in the intervention group experienced significantly less physical fatigue at 18 wk and general fatigue at 36 wk (mean between group differences, -3.2; 95% confidence interval [CI], -6.2 to -0.2; effect size [ES], -0.9 and -2.7; 95% CI, -5.2 to -0.1; ES, -0.8, respectively), and reported higher physical functioning (12.3; 95% CI, 3.3-21.4; ES, 1.0) compared with patients in the usual care group. The Physical Activity During Cancer Treatment trial shows that an 18-wk supervised exercise program in colon cancer patients during chemotherapy is safe and feasible. The intervention significantly reduced physical fatigue at 18 wk and general fatigue at 36 wk. Considering the number of patients included in the present study, replication in a larger study population is required.

Reappraisal of Total Pancreatectomy in 45 Patients With Pancreatic Ductal Adenocarcinoma in the Modern Era Using Matched-Pairs Analysis: Multicenter Study Group of Pancreatobiliary Surgery in Japan.

The aim of this study was to reappraise the clinical role of total pancreatectomy with curative intent in patients with pancreatic ductal adenocarcinoma (PDAC). In 2001 to 2011 database from 7 institutions in Japan, 45 (3.1%) of 1451 patients with PDAC underwent total pancreatectomy (TP group), and 885 patients underwent pancreaticoduodenectomy (PD group). A matched-pairs group consisted of 45 patients matched for age, sex, year, resectability status, and neoadjuvant therapy (matched-PD group). Clinicopathological data, overall survival, and disease-free survival were compared between groups. Clinical features of the TP group revealed higher-stage disease, greater surgical stress, a higher frequency of lymph node metastasis, and a lower adjuvant chemotherapy completion rate compared with the PD group (P < 0.05). Overall survival and disease-free survival in the TP group were significantly worse than those in the PD group (P < 0.05). Multivariate analysis revealed resectability status, neoadjuvant therapy, blood transfusion, lymph node metastasis, and adjuvant therapy to be significant prognostic factors. No differences in mortality and morbidity rates were observed between the 2 groups. A matched-pairs analysis revealed similar surgical outcomes and overall survival. The surgical outcome of total pancreatectomy for patients with PDAC is acceptable. When margin-negative resection is expected, total pancreatectomy should not be abandoned in the modern era.

Completion rates of intraperitoneal chemotherapy for stage III epithelial ovarian cancer in a community integrated health care system

Completion rates of intraperitoneal chemotherapy for stage III epithelial ovarian cancer in a community integrated health care system

Concurrent hyperfractionated chemoradiotherapy for head and neck squamous cell carcinoma: the prognostic impact of the overall treatment time and completion rates of chemotherapy.

The purpose of this study was to investigate whether the overall treatment time and completion rates of chemotherapy were predictive factors for the survival rates in patients with squamous cell carcinoma of the head and neck (SCCHN) who were treated with concurrent chemoradiotherapy (CCRT) using hyperfractionated radiotherapy (RT) and daily carboplatin. The number of intermission days of RT were as follows; 0 (n = 37), 1–5 (n = 8), 6–10 (n = 12) and ≥11 (n = 12), and the days of RT without carboplatin; 0 (n = 27), 1–5 (n = 13), 6–10 (n = 13) and ≥7 (n = 16). The overall treatment time (≤48 vs ≥49 days) was a significant prognostic factor for the local control, disease-free survival and overall survival rates. The completion rate of chemotherapy, as the number of days of RT without carboplatin, was not a significant factor affecting any of the survival rates. In discussion, the strengths of the present study contain that all the patients were treated with 72 Gy delivered as 1.2 Gy twice daily, and received concurrent chemotherapy comprising daily carboplatin as a radio-sensitizer. Based on the results, the completion rate of chemotherapy may have a lower impact on the local control rate in comparison with the overall treatment time. We believe that when a treatment interruption is needed because of the acute toxicities, hyperfractionated RT should be resumed as soon as possible independently while continuing the break of daily carboplatin. The overall treatment time influenced the clinical outcomes in SCCHN patients treated with hyperfractionated CCRT using carboplatin, while the impact of the completion rates of daily carboplatin was limited. Sixty-nine consecutive patients with SCCHN were initially treated with definitive CCRT and were retrospectively analyzed. All 69 patients were treated with CCRT using hyperfractionated RT of 72 Gy in 60 fractions and daily carboplatin (25 mg/m2). The patients treated with other chemotherapeutic regimens or induction chemotherapy were excluded. On the intermission days of the RT, carboplatin was not prescribed. After the intermission, CCRT using RT plus daily carboplatin or RT alone was resumed.

Impact of early disease progression and surgical complications on adjuvant chemotherapy completion rates and survival in patients undergoing the surgery first approach for resectable pancreatic ductal adenocarcinoma – A population-based cohort study

Background. Multimodality treatment (MMT) improves survival for patients with pancreatic ductal adenocarcinoma (PDAC). The surgery-first (SF) strategy is the most universally accepted approach.Material and methods. Population-based retrospective cohort study of all cases of resectable PDAC from 2006 to 2012. Patients were planned for adjuvant chemotherapy (AC) with the Nordic 5-fluorouracil/leucovorin regimen. Reasons for and rates of failure to complete AC, postoperative major complications (PMC), and overall survival (OS) were analysed.Results. Of 203 patients, 85 (41.9%) completed AC, 41 (20.2%) failed to complete AC, and 77 (37.9%) never initiated AC. Primary reasons for not initiating or completing AC were early disease progression (34.7%), postoperative complications/poor performance status (32.2%), and age > 75 years (24.6%). Median OS in the whole cohort was 17.0 months, and 20.0 months in patients who initiated AC. Median OS in patients who completed AC was higher than in patients who did not (25.0 months vs. 12.0 months, p < 0.001). PMC (n = 41) were associated with decreased initiation rate (p < 0.001) and completion rate (p = 0.007) of AC, and decreased median OS (11.0 months vs. 19.0 months, p = 0.028). Among patients with R1 resection, PMC again were associated with worse median OS (8.0 months vs. 16.0 months, p = 0.028). Multivariate analysis demonstrated that completion of MMT and tumour grade (G1/G2) were related to mortality rate (p < 0.001). Mortality risk for patients who completed AC was reduced also when adjusting for competing risk (SHR 0.426, p < 0.001).Conclusions. MMT completion is strongly associated with reduced mortality risk in patients with resectable PDAC undergoing the SF approach. Early disease progression and PMC/poor performance status preclude MMT completion in more than one third of the patients. These reasons for failure to complete MMT underscore the need for strategies to improve patient selection and reduce surgical morbidity in patients with resectable PDAC.

An Exercise Intervention During Chemotherapy for Women With Recurrent Ovarian Cancer: A Feasibility Study.

The aim of this study was to determine the feasibility of a combined supervised and home-based exercise intervention during chemotherapy for women with recurrent ovarian cancer. Secondary aims were to determine the impact of physical activity on physical and psychological outcomes and on chemotherapy completion rates. Women with recurrent ovarian cancer were recruited from 3 oncology outpatient clinics in Sydney and Canberra, Australia. All participants received an individualized exercise program that consisted of 90 minutes or more of low to moderate aerobic, resistance, core stability, and balance exercise per week, for 12 weeks. Feasibility was determined by recruitment rate, retention rate, intervention adherence, and adverse events. Aerobic capacity, muscular strength, fatigue, sleep quality, quality of life, depression, and chemotherapy completion rates were assessed at weeks 0, 12, and 24. Thirty participants were recruited (recruitment rate, 63%), with a retention rate of 70%. Participants averaged 196 ± 138 min · wk of low to moderate physical activity throughout the intervention, with adherence to the program at 81%. There were no adverse events resulting from the exercise intervention. Participants who completed the study displayed significant improvements in quality of life (P = 0.017), fatigue (P = 0.004), mental health (P = 0.007), muscular strength (P = 0.001), and balance (P = 0.003) after the intervention. Participants completing the intervention had a higher relative dose intensity than noncompleters (P = 0.03). A program consisting of low to moderate exercise of 90 min · wk was achieved by two-thirds of women with recurrent ovarian cancer in this study, with no adverse events reported. Randomized control studies are required to confirm the benefits of exercise reported in this study.

Comparison of two types of digestive tract reconstruction after total gastrectomy in patients with gastric carcinoma

To evaluate the influence of two different types of digestive tract reconstruction on the life quality, nutritional status and tolerance to adjuvant chemotherapy after total gastrectomy in patients with gastric carcinoma. The clinical data of a total of 107 patients treated in our department from January 2005 to december 2008 were analyzed retrospectively. Among them, 49 patients underwent digestive tract reconstruction with functional jejunal interposition (FJI group) and 58 patients underwent Roux en-Y jejunal P-type anastomosis (PR group) after total gastrectomy. 79 of 107 (73.8%) patients received postoperative adjuvant chemotherapy with XELOX regimen. The digestive complications and tolerance to chemotherapy were assessed respectively. Neither severe complications nor surgery-related or chemotherapy-related death were observed among the 107 patients. There were statistical differences in the incidence rate of emaciation, dumping syndrome and retention syndrome between the FJI and PR groups (P < 0.05), but no significant statistical difference in incidence rate of reflux esophagitis (P > 0.05). 28 of 40 (70.0%) patients in the FJI group completed all six cycles of chemotherapy, while 12 (30.0%) patients interrupted the treatment due to chemotherapy-related toxicity. 39 patients in the PR group received chemotherapy, 19 (48.7%) of them completed 6 cycles of chemotherapy but 20 (51.3%) patients interrupted. There was a significant difference in the incidence rate of grade III/IV chemotherapeutic toxicity and completion rate of chemotherapy (P < 0.05). Both functional jejunal interposition and Roux-Y operation are reasonable and safe procedures of digestive tract reconstruction. The incidence rates of emaciation, dumping syndrome and retention syndrome are lower in the patients with FJI, showing a better tolerance to adjuvant chemotherapy than Roux en-Y jejunal p type anastomosis.

Low completion rate of adjuvant chemotherapy in resected pancreatic cancer in clinical routine care

The microscale transport and stream model MITRAS has been improved and a new technique has been implemented to improve numerical stability for complex obstacle configurations. Results of the updated version have been compared with wind tunnel data using an evaluation method that has been established for simple obstacle configurations. MITRAS is a part of the M-SYS model system for the assessment of ambient air quality. A comparison of model results for the flow field against quality ensured wind tunnel data has been carried out for both idealised and realistic test cases. Results of the comparison show a very good agreement of the wind field for most test cases and identify areas of possible improvement of the model. The evaluated MITRAS results can be used as input data for the M-SYS microscale chemistry model MICTM. This paper describes how such a comparison can be carried out for simple as well as realistic obstacle configurations and what difficulties arise.

PWE-195 The enhanced recovery programme does not influence adjuvant chemotherapy rates following major pancreatic and liver resection surgery

Introduction The Enhanced Recovery Programme (ERP) has been shown to improve postoperative complications and reduce hospital stay in patients undergoing major HPB surgical oncological resections. 1 The ERP should allow more patient autonomy in their care and extend beyond the current hospital admission. The benefits of the ERP following hospital discharge are unclear, particularly with regards to adjuvant chemotherapy completion rates. Method A retrospective study was designed looking at the effect of the ERP on adjuvant chemotherapy rates following major pancreatic and liver resections. Patients deemed suitable for curative oncological resection surgery were included in the study. Neo-adjuvant and adjuvant chemotherapy regimens were decided as per the multidisciplinary team decision. Patients in the ERP group who didn’t complete the ERP protocol were analysed in the EPR group on an intention-to-treat basis. Results Between 2005 and 2013, 222 patients (100 liver resections and 122 pancreatic resections; median age 66 years, 1.4:1 male:female ratio) were identified and included in the study, with 142 patients (64.0%) following the ERP protocol. Two-thirds of patients in the ERP group successfully completed the ERP protocol. The ERP did not influence the time to chemotherapy (p = 0.14 pancreas group; p = 0.23 liver group) or successful completion of at least 6 cycles of chemotherapy (0.42 pancreas group; p = 0.06 liver group). Conclusion The ERP has been shown to benefit patients in the immediate postoperative period, with a shorter hospital stay. The results of this study suggest that the benefit of the ERP following hospital discharge is limited and, in particular, does not affect the uptake or successful completion of adjuvant chemotherapy. The effect of the ERP on long-term outcome and cancer-specific survival is, however, still unclear. The ERP following major resection should be further developed to include a stronger community and primary care component to help facilitate care after discharge. Disclosure of interest None Declared. Reference . Jones C, Kelliher L, Dickinson M, et al . Randomized clinical trial on enhanced recovery versus standard care following open liver resection. Br J Surg. 2013July;100(8):1015–1024.

Effect of Low-Intensity Physical Activity and Moderate- to High-Intensity Physical Exercise During Adjuvant Chemotherapy on Physical Fitness, Fatigue, and Chemotherapy Completion Rates: Results of the PACES Randomized Clinical Trial.

We evaluated the effectiveness of a low-intensity, home-based physical activity program (Onco-Move) and a moderate- to high-intensity, combined supervised resistance and aerobic exercise program (OnTrack) versus usual care (UC) in maintaining or enhancing physical fitness, minimizing fatigue, enhancing health-related quality of life, and optimizing chemotherapy completion rates in patients undergoing adjuvant chemotherapy for breast cancer. We randomly assigned patients who were scheduled to undergo adjuvant chemotherapy (N = 230) to Onco-Move, OnTrack, or UC. Performance-based and self-reported outcomes were assessed before random assignment, at the end of chemotherapy, and at the 6-month follow-up. We used generalized estimating equations to compare the groups over time. Onco-Move and OnTrack resulted in less decline in cardiorespiratory fitness (P < .001), better physical functioning (P ≤ .001), less nausea and vomiting (P = .029 and .031, respectively) and less pain (P = .003 and .011, respectively) compared with UC. OnTrack also resulted in better outcomes for muscle strength (P = .002) and physical fatigue (P < .001). At the 6-month follow-up, most outcomes returned to baseline levels for all three groups. A smaller percentage of participants in OnTrack required chemotherapy dose adjustments than those in the UC or Onco-Move groups (P = .002). Both intervention groups returned earlier (P = .012), as well as for more hours per week (P = .014), to work than the control group. A supervised, moderate- to high-intensity, combined resistance and aerobic exercise program is most effective for patients with breast cancer undergoing adjuvant chemotherapy. A home-based, low-intensity physical activity program represents a viable alternative for women who are unable or unwilling to follow the higher intensity program.

Hangeshashinto Improves the Completion Rate of Chemoradiotherapy and the Nutritional Status in Patients with Head and Neck Cancer

Purpose: Severe oral and pharyngeal mucositis is one of the most critical toxicities known to lead to the discontinuation of chemoradiotherapy (CRT) for head and neck cancer (HNC). Hangeshashinto (TJ-14) is a Kampo medicine that relieves chemotherapy-induced oral mucositis. We investigated the effect of TJ-14 on mucositis, nutritional status, and the completion rate of CRT. Methods: The study group comprised patients with advanced HNC who were treated with concomitant weekly cisplatin and 70 Gy of radiotherapy. The primary endpoint was the completion rate of chemotherapy, and the secondary endpoints were the grade of mucositis and the nutritional status. Results: A total of 57 patients were included in this study. The completion rate of CRT among patients who were treated with TJ-14 was 91.4%. There was a significant difference in the completion rate of CRT between the groups treated with and without TJ-14 (p = 0.0452). The reduction in body weight was significantly improved from 10.89 to 5.89% with TJ-14 administration (p = 0.003), and the reduction in serum albumin was also significantly decreased from 17.37 to 8.73%. (p = 0.024). Conclusion: This therapy allowed a high completion rate of CRT as well as significant benefits in terms of nutritional status. We plan to carry out a further large-scale study of TJ-14.

Cost-utility comparison of neoadjuvant chemotherapy versus primary debulking surgery for treatment of advanced-stage ovarian cancer in patients 65 years old or older

Treatment for advanced-stage epithelial ovarian cancer (AEOC) includes primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT). A randomized controlled trial comparing these treatments resulted in comparable overall survival (OS). Studies report more complications and lower chemotherapy completion rates in patients 65 years old or older receiving PDS. We sought to evaluate the cost implications of NACT relative to PDS in AEOC patients 65 years old or older. A 5 year Markov model was created. Arm 1 modeled PDS followed by 6 cycles of carboplatin and paclitaxel (CT). Arm 2 modeled 3 cycles of CT, followed by interval debulking surgery and then 3 additional cycles of CT. Parameters included OS, surgical complications, probability of treatment initiation, treatment cost, and quality of life (QOL). OS was assumed to be equal based on the findings of the international randomized control trial. Differences in surgical complexity were accounted for in base surgical cost plus add-on procedure costs weighted by occurrence rates. Hospital cost was a weighted average of diagnosis-related group costs weighted by composite estimates of complication rates. Sensitivity analyses were performed. Assuming equal survival, NACT produces a cost savings of $5616. If PDS improved median OS by 1.5 months or longer, PDS would be cost effective (CE) at a $100,000/quality-adjusted life-year threshold. If PDS improved OS by 3.2 months or longer, it would be CE at a $50,000 threshold. The model was robust to variation in costs and complication rates. Moderate decreases in the QOL with NACT would result in PDS being CE. A model based on the RCT comparing NACT and PDS showed NACT is a cost-saving treatment compared with PDS for AEOC in patients 65 years old or older. Small increases in OS with PDS or moderate declines in QOL with NACT would result in PDS being CE at the $100,000/quality-adjusted life-year threshold. Our results support further evaluation of the effects of PDS on OS, QOL and complications in AEOC patients 65 years old or older.

Abstract CT303: A multicenter phase ii study of adjuvant chemotherapy with oral fluoropyrimidine s-1 for non-small-cell lung cancer

Abstract Background: S-1, registered as “Teysuno” in European countries, is a novel oral fluoropyrimidine derivative consisting of tegafur (FT) and 2 modulators, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo). FT is a prodrug of 5-fluorouracil (5-FU) and CDHP is a reversible competitive inhibitor of dihydropyrimidine dehydrogenase (DPD), an enzyme involved in the degradation of 5-FU. Although S-1 is used for chemotherapy of gastric cancers, the use of S-1 for the treatment of lung cancer is so far limited. Here, we conducted a feasibility study for using S-1 as a postoperative chemotherapy in 50 patients with curatively resected stage IB-IIIA non-small-cell lung cancer. Patients and Methods: Adjuvant chemotherapy consisted of 8 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg per day. Fifty-one patients from 7 institutions were enrolled in this pilot study, from June 2005 to March 2007. The primary end point was the completion rate of scheduled adjuvant chemotherapy. Secondary end points were the incidence and grade of adverse reactions. The Kaplan-Meier method was used to estimate overall survival (OS) and relapse-free survival (RFS). The log-rank test was used to assess the differences between groups.The impacts of 19 clinicopathological factors including EGFR mutation status and immunohistochemical expressions of 5-FU metabolizing enzymes of the resected cancers on survival were analyzed. Results: Fifty patients were eligible for the study (Pathological stage; IB; n=28, IIA; n=10, IIB; n=5, IIIA; n=7). The completion rate for the planned 8 courses of S-1 administration was 72.0% (36 patients). Total percentage administration amount was 71.1%. Grade 3 adverse reactions such as neutropenia (4.0%), anorexia (4.0%), thrombopenia (2.0%), anemia (2.0%), elevated total bilirubin (2.0%), hypokalemia (2.0%), nausea (2.0%), and diarrhea (2.0%) were observed, but no grade 4 adverse effects were encountered. OS and RFS rates at 5 years were 72.5% and 67.5%, respectively. Among the 19 clinicopathological factors, lymphatic and vessel invasion correlated with the low RFS rate (p&amp;lt;0.05). The OS rate of the patients with squamous cell carcinoma was lower than that of adenocarcinoma (p&amp;lt;0.05). The multivariate analysis indicated high T factors (T2 or more) and immunohistochemically low thymidine synthase expression were correlated with low RFS rates. EGFR mutation status did not affect survival. In cases of recurrence, platinum doublet was mostly selected for further treatment. Conclusion: Postoperative 1-year administration of S-1 seems feasible as oral adjuvant chemotherapy for lung cancer. The oral formulation and low incidence of adverse reactions permit treatment on an outpatient basis. Survival analysis revealed that this protocol might have significant potential at the adjuvant setting. Citation Format: Tomoshi Tsuchiya, Naoya Yamasaki, Keitaro Matsumoto, Takuro Miyazaki, Takeshi Nagayasu. A multicenter phase ii study of adjuvant chemotherapy with oral fluoropyrimidine s-1 for non-small-cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT303. doi:10.1158/1538-7445.AM2014-CT303

The initial report of RTOG 0524: Phase I/II trial of a combination of paclitaxel and trastuzumab with daily irradiation or paclitaxel alone with daily irradiation following transurethral surgery for noncystectomy candidates with muscle-invasive bladder cancer.

LBA287 Background: Most patients (pts) with muscle-invasive bladder urothelial carcinoma (UC) undergo definitive local treatment with radical cystectomy. Up to 50% of pts with UC overexpress HER2/neu, which may be associated with reduced responsiveness to chemoradiation and reduced survival. Many pts with UC have comorbidities that preclude surgery, creating a traditionally underserved population with worse outcomes. RTOG 0524 evaluated the safety and efficacy of trimodality, organ-preserving therapy in pts not suitable for cystectomy. Methods: Pts with invasive bladder UC (stages T2-T4a, N0-1, M0) underwent cystoscopic tumor resection. Tumors were analyzed by HER2/neu immunohistochemistry (IHC) and assigned to chemotherapy group I (IHC 2+ or 3+; paclitaxel and trastuzumab) or II (IHC negative or 1+; paclitaxel alone). Concurrent weekly paclitaxel (50 mg/m2), weekly trastuzumab (group I only) and daily radiation (64.8 Gy total in 36 fractions) were given for seven consecutive weeks. Results: 21 eligible patients were entered in group I and 47 in group 2, with median ages of 80 and 73, respectively. The primary endpoint was acute protocol-defined toxicity related to treatment. Acute toxicity was observed in 7/21 pts (33%) in group I and 14/47 pts (30%) in group II. Most common grade &gt; 3 adverse events in groups I and II were marrow suppression (43% and 17%), diarrhea (33% and 30%), and hyponatremia (14% and 4%). Three deaths on study were attributed to colonic perforation, pneumonia, and sudden death. Radiation completion rates were 72% and 85% in the two groups, and full-dose chemotherapy completion rates were 52% and 51%. Evaluation by cystoscopy and/or tumor biopsy at 12 weeks noted complete response in 9/13 pts (69%) in group I, in 19/33 pts (58%) in group II, and was not performed in the remaining pts. Conclusions: Trimodality bladder-preserving therapy is an appropriate treatment in noncystectomy candidates with invasive UC. The response rate for HER2/neu-targeted therapy is encouraging but may increase certain adverse events in this challenging population. Clinical trial information: NCT00238420.

Effect of Laparoscopic Surgery on the Initiation and Completion of Chemotherapy in Patients With Colon Cancer

See Article on Page 274-279 The developments in colon cancer treatment over the past two decades can be found largely in chemotherapy and laparoscopic surgery. Adjuvant chemotherapy increases survival in stage III and select stage II colon cancer patients [1, 2]. Reports in the literature have indicated that delaying the initiation of adjuvant chemotherapy for longer than eight weeks after surgery or after failure to complete adjuvant chemotherapy adversely affects the overall survival of colon cancer patients [3, 4]. Laparoscopic surgery has several benefits in cosmesis, postoperative length of hospital stay, analgesics usage and return of bowel function while it is comparable in survival to open surgery. Therefore, many large-volume centers use laparoscopic surgery as the mainstay in colon cancer treatment. However, few studies deal with the effect of laparoscopic surgery on the initiation or completion of adjuvant chemotherapy in colon cancer patients. In a previous study [5], only 67% of patients were reported to have completed their chemotherapy. If those effects of laparoscopic surgery are proven, some chance may exist to improve colon cancer survival by increasing compliance with chemotherapy. Recently, Gantt Jr et al. [6] reported no difference in proportions of patients who received adjuvant chemotherapy more than eight weeks after surgery between the laparoscopic and the open surgery groups. Their notable finding was that the delay in the initiation of adjuvant chemotherapy adversely affected patients' disease-free and overall survival in the open surgery group, but not in both of the laparoscopic surgery group. Although the article has several limitations and shortcomings, vague follow-up period, uncertainty of whether cancer-specific survival was calculated or not, unclear relationship between chemotherapy completion rate and survival, no significant difference in the chemotherapy completion rate and a significant difference in survival rate between the laparoscopic surgery and the open surgery groups were noted [7]. Further studies dealing with the issue of laparoscopic surgery and chemotherapy compliance are expected to be spurred by the publication of this study.