Early Tumor Shrinkage and Depth of Response as Predictors of Survival for Advanced Biliary Tract Cancer: An Exploratory Analysis of JCOG1113.

BACKGROUND: Recent studies suggest that early tumor shrinkage (ETS) and depth of response (DpR) reflect outcomes of chemotherapy in various cancers. This study evaluated the association of ETS and DpR with clinical outcomes using data from JCOG1113, which demonstrated the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for chemotherapy-naïve advanced biliary tract cancer. MATERIAL AND METHODS: In total, 354 (289 with measurable target lesions) patients enrolled in JCOG1113 were divided into ETS-unachieved and ETS-achieved groups (≥20% tumor reduction at week 6) and DpR-low and DpR-high groups (≥40% maximum shrinkage) until 12 weeks after enrollment. The impact of ETS and DpR on survival outcome was evaluated using the multivariable Cox proportional hazard model. RESULTS: The proportions of patients in the ETS-achieved and DpR-high groups were similar between the 2 treatment arms. The hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) for the ETS-achieved group were 0.70 (95% confidence interval (CI), 0.52-0.93) and 0.60 (95%CI, 0.44-0.81), respectively. The HRs of PFS and OS for the DpR-high group were 0.67 (95%CI, 0.48-0.94) and 0.64 (95%CI, 0.46-0.90), respectively. In the subpopulation treatment effect pattern plot analysis, most patients in the ETS-achieved group in the GC arm did not experience disease progression after 12 weeks from the landmark. CONCLUSION: As on-treatment markers, ETS and DpR were effective tools. ETS was clinically useful, because it can be used to evaluate the outcomes of treatment early at a specific time.

Canadian monitoring program of the surface contamination with 11 antineoplastic drugs in 124 centers.

INTRODUCTION: Occupational exposure to antineoplastic drugs can lead to long-term adverse effects on workers' health. A reproducible Canadian surface monitoring program was established in 2010. The objective was to describe contamination with 11 antineoplastic drugs measured on 12 surfaces among hospitals participating in this annual monitoring program. METHODS: Each hospital sampled six standardized sites in oncology pharmacies and six in outpatient clinics. Ultra-performance liquid chromatography coupled with tandem mass spectrometry was used for cyclophosphamide, docetaxel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, irinotecan, methotrexate, paclitaxel, and vinorelbine. Platinum-based drugs were analyzed by inductively coupled plasma mass spectrometry; this excludes inorganic platinum from the environment. Hospitals filled out an online questionnaire about their practices; a Kolmogorov-Smirnov test was used for some practices. RESULTS: One hundred and twenty-four Canadian hospitals participated. Cyclophosphamide (405/1445, 28%), gemcitabine (347/1445, 24%), and platinum (71/756, 9%) were the most frequent. The 90th percentile of surface concentration was 0.01 ng/cm² for cyclophosphamide and 0.003 ng/cm² for gemcitabine. Centers that prepared 5000 or more antineoplastic per year had higher concentrations of cyclophosphamide and gemcitabine on their surfaces (p = 0.0001). Almost half maintained a hazardous drugs committee (46/119, 39%), but this did not influence the cyclophosphamide contamination (p = 0.051). Hazardous drugs training was more frequent for oncology pharmacy and nursing staff than for hygiene and sanitation staff. CONCLUSIONS: This monitoring program allowed centers to benchmark their contamination with pragmatic contamination thresholds derived from the Canadian 90th percentiles. Regular participation and local hazardous drug committee involvement provide an opportunity to review practices, identify risk areas, and refresh training.

Canadian monitoring program of the surface contamination with 11 antineoplastic drugs in 122 centers.

INTRODUCTION: Occupational exposure to antineoplastic drugs can lead to long-term adverse effects on workers' health. Environmental monitoring is conducted once a year, as part of a Canadian monitoring program. The objective was to describe contamination with 11 antineoplastic drugs measured on surfaces. METHODS: Six standardized sites in oncology pharmacy and six in outpatient clinic were sampled in each hospital. Samples were analyzed by ultra-performance liquid chromatography coupled with tandem mass spectrometry (non-platinum drugs) and by inductively coupled plasma mass spectrometry (platinum-based drugs). The limits of detection (in ng/cm2) were: 0.0006 for cyclophosphamide; 0.001 for docetaxel; 0.04 for 5-fluorouracil; 0.0004 for gemcitabine; 0.0007 for irinotecan; 0.0009 for methotrexate; 0.004 for paclitaxel, 0.009 for vinorelbine, 0.02 for doxorubicine, 0.0037 for etoposide and 0.004 for the platinum. Sub-analyses were done with a Kolmogorov-Smirnov test. RESULTS: 122 Canadian hospitals participated. Cyclophosphamide (451/1412, 32% of positive samples, 90th percentile of concentration 0.0160 ng/cm2) and gemcitabine (320/1412, 23%, 0.0036 ng/cm2) were most frequently measured on surfaces. The surfaces most frequently contaminated with at least one drug were the front grille inside the biological safety cabinet (97/121, 80%) and the armrest of patient treatment chair (92/118, 78%).The distribution of cyclophosphamide concentration was higher for centers that prepared ≥ 5000 antineoplastic drug preparations/year (p < 0.0001). CONCLUSIONS: This monitoring program allowed centers to benchmark their contamination with pragmatic contamination thresholds derived from the Canadian 90th percentiles. Problematic areas need corrective measures such as decontamination. The program helps to increase the workers' awareness.

Comparing the Efficacy and Safety of Gemcitabine plus Nab-Paclitaxel versus Gemcitabine Alone in Older Adults with Unresectable Pancreatic Cancer.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) has been a standard treatment for unresectable pancreatic cancer (uPC); however, the current treatment status and usefulness in older adults with uPC remain unclear. Therefore, we aimed to investigate the patient background and compare the efficacy and safety of GnP versus other treatments in older adults with uPC. PATIENTS AND METHODS: In this prospective observational study, we enrolled 233 eligible patients aged ≥76 years with pathologically proven, clinically uPC, and no history of chemotherapy from 55 Japanese centers during September 2018-September 2019. The main endpoints were overall survival (OS), progression-free survival (PFS), and safety. Geriatric assessments were performed upon registration and after 3 months. To adjust for confounders, we conducted propensity score-matched analyses. RESULTS: GnP, gemcitabine alone (Gem), best supportive care, and other therapies were administered to 116, 72, 16, and 29 patients, respectively. In the propensity score-matched analysis, 42 patients each were selected from the GnP and Gem groups. The median OS was longer in the GnP group than in the Gem group (12.2 vs. 9.4 months; hazard ratio [HR], 0.65; 95% CI, 0.37-1.13). The median PFS was significantly longer in the GnP group than in the Gem group (9.2 vs. 3.7 months; HR, 0.38; 95% CI, 0.23-0.64). The incidence of severe adverse events was higher with GnP than with Gem; however, the difference was not significant. CONCLUSION: GnP is more efficacious than Gem in patients aged ≥76 years with uPC despite demonstrating a higher incidence of severe adverse events.

Safety and Efficacy of Gemcitabine Plus Nab-Paclitaxel for Metastatic Pancreatic Cancer Patients Undergoing Biliary Stent Placement.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) is the first-line chemotherapeutic regimen for metastatic pancreatic cancer (MPC); however, there are concerns regarding its safety in patients undergoing biliary stent placement. This study aimed to examine the tolerability and efficacy of GnP in MPC patients who underwent biliary stent placement. METHODS: A total of 105 MPC patients who had received GnP treatment between 2015 and 2020 were included and investigated. The patients were divided into two groups: those undergoing biliary stent placement for symptomatic biliary obstruction (BO) (With-BO group) and those without biliary stent placement (Without-BO group). The best tumor response, overall survival (OS), and adverse events in each group were compared. RESULTS: The partial response, stable disease, and progressive disease rates were 22%, 61%, and 14.6% in the With-BO group, and 26.6%, 46.9%, and 21.9% in the Without-BO group, respectively, with no significant differences. The median OS was 12.2 months and 14.6 months in the With-BO and Without-BO groups, respectively (P = 0.483). Grade 3 or higher biliary tract-related events were significantly more common in the With-BO group (41.5%) than in the Without-BO group (1.6%) (P < 0.001), but all events were managed successfully by urgent intervention. The rates of any treatment-related toxicities, including febrile neutropenia, were not significantly different, and there were no chemotherapy-related deaths in either group. CONCLUSIONS: GnP can be as tolerable and effective in MPC patients with biliary stents as in those without biliary stents. However, careful management and appropriate reintervention to treat biliary tract-related adverse events are required.

Meta-analysis and indirect treatment comparison of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel as first-line chemotherapy in advanced pancreatic cancer.

BACKGROUND: Modified FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NAB) have been recommended as first-line therapies for advanced pancreatic cancer (PC). Due to the lack of evidence to directly compare them, we conducted this network meta-analysis to indirectly compare the effectiveness and toxicity of modified FOLFIRINOX and GEM-NAB. METHODS: The eligible retrospective studies on treatments related to modified FOLFIRINOX and GEM-NAB up to 4 April 2020 were searched and assessed. We used the frequentist model to analyze the survival and toxicity data between different treatments. Pooled analysis for overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and events of toxicity were analyzed in this study. RESULTS: Twenty-two studies were involved in this network meta-analysis. The comparisons on OS and PFS showed that modified FOLFIRINOX and GEM-NAB had similar treatment efficacy (OS: 1.13; 95% CI: 0.78-1.63; PFS: HR: 1.19; 95% CI: 0.85-1.67). GEM-NAB was more effective than modified FOLFIRINOX based on the result of ORR (RR: 1.43; 95% CI: 1.04-1.96). Moreover, our analysis showed a similar toxicity profile between modified FOLFIRINOX and GEM-NAB. CONCLUSIONS: The current evidence showed that modified FOLFIRINOX and GEM-NAB were similar in survival and toxicity. Many factors should be considered for in the formulation of optimal treatment, and our meta-analysis could provide some guidance to treatment selection in the first-line setting for advanced PC.

[Evaluation of the efficacy and safety of combination of gemcitabine and nedaplatin for patients with HER-2 negative metastatic breast cancer].

Objective: To assess the therapeutic efficacy and safety of the gemcitabine combined with nedaplatin (GN) chemotherapy for metastatic human epidermal growth factor receptor-2 (HER-2) negative breast cancer patients. Methods: Forty-five patients with HER-2 negative recurrent metastatic breast cancer who had received prior adjuvant or neoadjuvant therapy with anthracycline and/or taxanes were enrolled. All the patients received GN regime from January 2014 to February 2019. The therapeutic efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST) 1.1. The adverse response was evaluated and monitored according to common terminology criteria for adverse events (CTCAE). The progression-free survival (PFS) and overall survival (OS) and prognostic factors were also analyzed. Results: All of the 45 patients received 4 course GN, 1 of them achieved complete response, 21 achieved partial response. The objective response rate was 48.9 (95% CI: 33.7%-64.1%). Grade 3-4 hematological toxicities include leukopenia occurred in 10 (22.2%) of patients, neutropenia in 13 (28.9%) patients, and thrombocytopenia in 8 (17.6%) patients. The grade 3-4 hematological toxicities mainly manifested as nausea and vomiting, and the incidence was 4.4% (2/45). Among the 45 patients, 34 died, the median PFS was 5.1 (95% CI: 3.9-6.1) months and the median OS was 17.6 (95% CI: 13.1-20.9) months. Conclusion: The combination of gemcitabine and nedaplatin is an effective and tolerable treatment for metastatic breast cancer patients previously treated with anthracyclines and/or taxanes.

Folfirinox versus gemcitabine-cisplatin combination as first-line therapy in treatment of pancreaticobiliary cancer

Background/aim: The purpose of this study was to compare efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine-cisplatin as first-line therapy in patients with pancreatic cancer. Materials and methods: Pancreaticobiliary cancer patients who had Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating greater severity of illness) were evaluated to receive folfirinox or gemcitabine plus cisplatin. The primary endpoints were progression-free and overall survival time. Safety analysis was also evaluated as secondary measures. Results: There were 32 patients in the folfirinox group and 36 patients in the gemcitabine-cisplatin group. The median overall survival was 18.1 months (7.5­28.7) in the folfirinox group as compared with 9.7 months (6.5­13) in the gemcitabine-cisplatin group (p = 0.009). Median progression-free survival was 16.2 months (9­23.4) in the folfirinox group and 6.9 months (6.1­7.6) in the gemcitabine- cisplatin group (p = 0.001). Conclusion: Folfirinox is an option for the first-line treatment of patients with pancreatic cancer and good performance status.

Clinical characteristics and blood/serum bound prognostic biomarkers in advanced pancreatic cancer treated with gemcitabine and nab-paclitaxel.

BACKGROUND: In recent years treatment options for advanced pancreatic cancer have markedly improved, and a combination regimen of gemcitabine and nab-paclitaxel is now considered standard of care in Sweden and elsewhere. Nevertheless, a majority of patients do not respond to treatment. In order to guide the individual patient to the most beneficial therapeutic strategy, simple and easily available prognostic and predictive markers are needed. METHODS: The potential prognostic value of a range of blood/serum parameters, patient-, and tumour characteristics was explored in a retrospective cohort of 75 patients treated with gemcitabine/nab-paclitaxel (Gem/NabP) for advanced pancreatic ductal adenocarcinoma (PDAC) in the South Eastern Region of Sweden. Primary outcome was overall survival (OS) while progression free survival (PFS) was the key secondary outcome. RESULT: Univariable Cox regression analysis revealed that high baseline serum albumin (> 37 g/L) and older age (> 65) were positive prognostic markers for OS, and in multivariable regression analysis both parameters were confirmed to be independent prognostic variables (HR 0.48, p = 0.023 and HR = 0.47, p = 0.039,). Thrombocytopenia at any time during the treatment was an independent predictor for improved progression free survival (PFS) but not for OS (HR 0.49, p = 0.029, 0.54, p = 0.073), whereas thrombocytopenia developed under cycle 1 was neither related with OS nor PFS (HR 0.87, p = 0.384, HR 1.04, p = 0.771). Other parameters assessed (gender, tumour stage, ECOG performance status, myelosuppression, baseline serum CA19-9, and baseline serum bilirubin levels) were not significantly associated with survival. CONCLUSION: Serum albumin at baseline is a prognostic factor with palliative Gem/NabP in advanced PDAC, and should be further assessed as a tool for risk stratification. Older age was associated with improved survival, which encourages further studies on the use of Gem/NabP in the elderly.

Successful treatment of gemcitabine-induced acute interstitial pneumonia with imatinib mesylate: a case report.

BACKGROUND: Gemcitabine is currently the standard chemotherapy for the adjuvant treatment of pancreatic cancer. This chemotherapeutic agent is generally well-tolerated, myelosuppression and gastrointestinal toxicity being common side effects. Nevertheless, gemcitabine-induced pulmonary toxicity has been rarely reported. Despite its low incidence, the spectrum of pulmonary injury is wide, including potentially fatal conditions. We report a case of acute interstitial pneumonia related to gemcitabine, completely solved with Imatinib Mesylate (IM). CASE PRESENTATION: The patient was a 69-year-old man, who developed a hypoxemic respiratory distress during adjuvant treatment with gemcitabine for stage IIA pancreatic cancer. The nonspecific diffuse alveolar involvement found on computed tomography (CT), together with the negative tests for infectious aetiology and the continuing severe respiratory failure despite a long course of broad-spectrum therapy, suggested gemcitabine-induced acute pneumonia as the most likely diagnosis. Thus, after the failure of steroids and all other conventional therapies, the patient was treated with imatinib mesylate on the basis of its activity in the management of graft-versus-host-induced lung fibrosis. A follow-up CT scan of chest one month later showed complete resolution of pneumonia. CONCLUSION: Despite the low frequency of serious pulmonary toxicity, gemcitabine widespread use warns clinicians to consider this life-threatening toxicity. The favourable clinical outcome with IM treatment was remarkable, warranting additional study of IM in the treatment of lung fibrosis.

FOLFOX-4 as second-line therapy after failure of gemcitabine and platinum combination in advanced gall bladder cancer patients.

OBJECTIVE: There is no standard second-line chemotherapy after progression on first-line therapy including gemcitabine and platinum combination in advanced gall bladder cancer patients. So this study was undertaken to assess the efficacy and safety of FOLFOX-4 regimen in this setting. METHODS: In this observational study, patients with performance status ≤2, who progressed on first-line therapy, were enrolled from May 2010 to June 2014. FOLFOX-4 based treatment was administered until progression, unacceptable toxicity or up to 12 cycles. RESULTS: A total of 66 patients were enrolled in this study. The median age of patients was 52.5 years (32-66 years),of which 24 (36.36%) were males and 42 (63.63%) were females. The median number of cycles could be given were 9.5 (2-12). Only 43.93% patients in this study completed full 12 cycles of chemotherapy. Sixteen patients (24.24%) in this study required the dose reduction at least in one cycle of chemotherapy due to toxicities. Disease control rate was seen in 39 (59.09%) patients, with complete response in none, partial response in 16 (24.24%), stable disease in 23 (34.84%) and progressive disease in 27 (40.90%) patients. The median progression free survival was 3.9 months; median overall survival was 7.6 months. The main Grade 3/4 side effects seen were hematological in 31.81% (n = 21) and gastrointestinal in 25.75% (n = 17) patients. Majority of patients (46%) had Grade 1/2 peripheral neuropathy. CONCLUSIONS: FOLFOX-4 is an effective and well-tolerated regimen as a second-line treatment in advanced gall bladder cancer patients. Further studies are required, especially in the Indian subcontinent.

Primary osteosarcoma of the uterine corpus: A case report.

Pure osteosarcoma arising from the uterus is extremely rare. Only 15 cases of this type of cancer have been reported to date. Most patients showed local or lung metastasis early after surgery and died within a year of treatment initiation, regardless of multimodality therapy, indicating that this tumor is aggressive with a poor prognosis. Herein, we report the first clinical experience treated with a combination of docetaxel and gemcitabine for local and lung metastasis from primary osteosarcoma of the uterus. Although the disease was considered stable after three cycles of treatment, new metastatic lesions appeared in the lungs after six cycles. The patient was asymptomatic for 13 months; however, she died two months after symptom recurrence. Our case demonstrates that a combined regimen of docetaxel and gemcitabine may be a sound therapeutic option to control primary osteosarcoma of the uterus.

[Diagnostics and treatment of cholangiocellular carcinoma]. / Diagnostik und Therapie des cholangiozellulären Karzinoms.

Cholangiocellular carcinoma (CCA) is the second most frequent primary liver carcinoma and is an aggressive tumor, which is mostly diagnosed in advanced stages. The overall survival is poor. Histpathological analysis of tumor biopsies or cytological analysis of biliary brushings can be used to confirm the diagnosis. A differentiation is made between distal, perihilar and intrahepatic CCA. The anatomical position determines the diagnostic and therapeutic strategy. Before diagnostic or therapeutic measures are undertaken it is essential to resolve biliary obstruction via endoscopic stenting or percutaneous biliary drainage. Depending on the tumor stage curative treatment options comprise radical surgical resection with hepaticojejunostomy or in selected cases liver transplantation. For intrahepatic or distal CCA liver transplantation is not indicated. In the palliative setting systemic chemotherapy with gemcitabine and cisplatin leads to a significant improvement in survival time.

Capecitabine plus gemcitabine in thymic epithelial tumors: final analysis of a Phase II trial.

BACKGROUND: A multi-institutional Phase II trial was initiated in 2005 to test the combination gemcitabine and capecitabine in patients with thymic epithelial malignancies (TETs). PATIENTS & METHODS: Patients with histologic confirmation of TET diagnosis by central review who had received >1 systemic chemotherapy treatment were included. Patients received oral capecitabine (650 mg/mq twice daily on days 1-14) and intravenous gemcitabine (1000 mg/mq on days 1 and 8 every 3 weeks). RESULTS: Of the 30 patients included (18 men, 12 women; median age: 57 years, range: 48-61 years), the majority (73%) had thymoma, and the remaining thymic carcinoma. Eight patients developed grade 3-4 neutropenia. A total of 12 patients had a response. Median progression-free survival was 11 months (range: 6.5-16.5). CONCLUSION: Capecitabine and gemcitabine is highly active in TETs.

Immunotherapy in Combination with Chemotherapy for Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks estrogen and progesterone receptors and does not overexpress the human epidermal growth factor receptor 2 (HER2). Previous treatment options for TNBC were limited to chemotherapy alone, resulting in a poor patient prognosis. In 2018, an estimated 2.1 million new cases of breast cancer were diagnosed globally, with the incidence increasing by 0.5% annually from 2014 to 2018. The exact prevalence of TNBC is difficult to determine because it is based on the absence of certain receptors and overexpression of HER2. Treatment options for TNBC include surgery, chemotherapy, radiation therapy, and targeted therapy. The available evidence suggests that combination immunotherapy using PD-1/PD-L1 inhibitors may be a promising treatment option for metastatic TNBC. In this review, we evaluated the efficacy and safety of different immunotherapies regimens for the treatment of TNBC. In many clinical trials, the overall response rate and survival were better in patients treated with these drug combinations than those treated with chemotherapy alone. Although definitive treatments are not within reach, efforts to gain a deeper understanding of combination immunotherapy have the potential to overcome the urge for safe and effective treatments.

Clinical outcome and safety profile of metastatic pancreatic cancer patients treated with more than six cycles of nab-paclitaxel plus gemcitabine.

The phase III MPACT trial demonstrated the superiority of gemcitabine plus nab-paclitaxel (NABGEM) versus gemcitabine alone in previously untreated patients with metastatic pancreatic cancer (mPC). The aim of this study was to evaluate the responses in terms of efficacy and safety in patients treated with more than 6 cycles of chemotherapy. From January 2015 to December 2018, patients with mPC receiving first-line treatment with NABGEM were included in a multicentre retrospective observational study. Exploratory analyses of efficacy and safety were performed. The cohort included 153 patients with performance status of 1. The median overall survival and progression-free survival were 20 months (hazard ratio [HR] 0.28, 95% confidence interval [CI]: 0.17-0.44) and 10 months (HR 0.24 95% CI: 0.16-0.38) respectively, in patients who received >6 cycles compared to 9 and 5 months in those treated with ≤6 cycles (p < 0.001). The disease control rate was 100% versus 56% in patients receiving >6 and ≤6 cycles, respectively. No progression of disease was recorded in patients who received >6 cycles. Grade 1 neuropathy and grade 3 neutropenia were more frequent in patients treated with >6 cycles compared to patients receiving ≤6 cycles (p = 0.01; p = 0.03, respectively). Dose reduction was necessary for 70.1% and 53.4% of patients treated with >6 or ≤6 cycles, whereas treatment interruption occurred in 37.1% and 21.6%, respectively. Our results confirmed the efficacy and safety of NABGEM in untreated mPC. In particular, we highlighted significant clinical efficacy in patients who received >6 cycles of chemotherapy compared to those who received ≤6 cycles, with manageable toxicity profile.

Randomized phase III study of gemcitabine, cisplatin plus S-1 versus gemcitabine, cisplatin for advanced biliary tract cancer (KHBO1401- MITSUBA).

BACKGROUND: Gemcitabine/cisplatin (GC) combination therapy has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). No randomized clinical trials have been able to demonstrate the survival benefit over GC during the past decade. In our previous phase II trial, adding S-1 to GC (GCS) showed promising efficacy and we aimed to determine whether GCS could improve overall survival compared with GC for patients with advanced BTC. METHODS: We performed a mulitcenter, randomized phase III trial across 39 centers. Enrolled patients were randomly allocated (1:1) to either the GCS or GC arm. The GCS regimen comprised gemcitabine (1000 mg/m2 ) and cisplatin (25 mg/m2 ) infusion on day 1 and 80 mg/m2 of S-1 on days 1-7 every 2 weeks. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS), response rate (RR), and adverse events (AEs). This study is registered with Clinical trial identification: NCT02182778. RESULTS: Between July 2014 and February 2016, 246 patients were enrolled. The median OS and 1-year OS rate were 13.5 months and 59.4% in the GCS arm and 12.6 months and 53.7% in the GC arm, respectively (hazard ratio [HR] 0.79, 90% confidence interval [CI]: 0.628-0.996; P = .046 [stratified log-rank test]). Median PFS was 7.4 months in the GCS arm and 5.5 months in the GC arm (HR 0.75, 95% CI: 0.577-0.970; P = .015). RR was 41.5% in the GCS arm and 15.0% in the GC arm. Grade 3 or worse AEs did not show significant differences between the two arms. CONCLUSIONS: GCS is the first regimen which demonstrated survival benefits as well as higher RR over GC in a randomized phase III trial and could be the new first-line standard chemotherapy for advanced BTC. To exploit the advantage of its high RR, GCS is now tested in the neoadjuvant setting in a randomized phase III trial for potentially resectable BTC.

Chemo-Immunotherapy Regimes for Recurrent or Metastatic Nasopharyngeal Carcinoma: A Network Meta-Analysis and Cost-Effectiveness Analysis.

Introduction: In 2021, two phase III clinical trials confirmed that toripalimab or camrelizumab combined with gemcitabine and cisplatin (TGP or CGP) provide more benefits in the first-line treatment of R/M NPC than GP. Fortunately, TGP and CGP were recently approved as first-line treatments for cases experiencing R/M NPC by the China National Medical Products Administration in 2021. However, due to the high cost and variety of treatment options, the promotion of chemo-immunotherapeutics in the treatment of R/M NPC remains controversial. Therefore, we performed a cost-effectiveness assessment of the two newly approved treatment strategies to assess which treatments provide the greatest clinical benefits at a reasonable cost. Methods: A cost-effectiveness analysis and network meta-analysis network meta-analysis was conducted based on the JUPITER-02 and CAPTAIN-first Phase 3 randomized clinical trials. A Markov model was expanded for the evaluation of the effectiveness and cost of TGP, CGP, and GP chemotherapy with a 10-years horizon and measured the health achievements in quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and life-years (LYs). We constructed a treatment strategy and other parameters based on two clinical trials and performed one-way and probabilistic sensitivity experiments for the evaluation of the uncertainty in the model. Results: For the model of patients with treatment-R/M NPC, TGP was associated with a total cost of $48,525 and 2.778 QALYs (4.991 LYs), leading to an ICER of $15,103 per QALY ($10,321 per LY) compared to CGP. On comparing the GP chemotherapy, we found TGP and CGP incurred substantial health costs, resulting in ICERs of $19,726 per QALY and $20,438 per QALY, respectively. The risk of adverse events (AEs) and the price of the drugs had significant impacts on the ICER. At the assumed willingness-to-pay (WTP) threshold of $35,673 per QALY, there were approximately 75.8 and 68.5% simulations in which cost-effectiveness was achieved for TGP and CGP, respectively. Conclusion: From the Chinese payer's perspective, TGP is more possible to be a cost-effective regimen compared with CGP and GP for first-line treatment of patients with R/M NPC at a WTP threshold of $35,673 per QALY.

Usefulness of the G8 Geriatric Assessment Tool as a Prognostic Factor in Gemcitabine Plus Nab-paclitaxel Combination Therapy for Elderly Patients with Pancreatic Cancer.

Introduction: The usefulness of various prognostic factors for advanced pancreatic cancer (APC) has been reported, but the number of elderly patients in these studies is disproportionately fewer than those in general practice. This study aimed to examine the prognostic factors for elderly patients with APC receiving gemcitabine plus nab-paclitaxel (GnP) considering the G8 geriatric assessment tool. Methods: We retrospectively analyzed 77 elderly (≥65 years old) patients with APC who received GnP as first-line chemotherapy at our hospital. We used the receiver operating characteristic curve to set the optimal cutoff value for G8. Univariate and multivariate Cox regression models were applied to study independent prognostic factors. Results: The progression-free survival was 5.5 months, and the overall survival (OS) was 12.0 months in all patients. The most optimal cutoff of G8 was 10.5. OS of G8 ≥10.5 patients was superior to that of G8 <10.5 patients (18.5 versus 8.0 months). Multivariate analysis showed that Eastern Cooperative Oncology Group performance status 1 (hazard ratio [HR] 3.00, p = 0.02), neutrophil-lymphocyte ratio ≥3.9 (HR 2.73, p = 0.03), and G8 geriatric assessment <10.5 (HR 5.38, p < 0.001) were independent negative prognostic factors. Conclusions: G8 is useful for predicting prognoses in elderly patients with APC receiving GnP.

Intravesical gemcitabine for non-muscle invasive bladder cancer: An abridged Cochrane Review.

PURPOSE: To assess the comparative effectiveness and toxicity of intravesical gemcitabine instillation for non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We performed a comprehensive literature search on 11 September 2020. We included RCTs in which participants received intravesical gemcitabine for primary or recurrent NMIBC. Two review authors independently assessed the included studies and extracted data for the primary outcomes (time to recurrence, time to progression, grade III to V adverse events) and the secondary outcomes (time to death from bladder cancer, time to death from any cause, grade I or II adverse events, and disease-specific quality of life). We performed statistical analyses using a random-effects model and rated the certainty of the evidence using GRADE. RESULTS: We found seven studies with 1,222 participants. Gemcitabine may reduce the risk of recurrence over time, but may have a similar effect on progression and grade III to V adverse events compared to saline. Gemcitabine may reduce recurrence and progression compared to mitomycin. We are uncertain about the effect of gemcitabine on the grade III to V adverse events compared to mitomycin. Gemcitabine may reduce recurrence and progression compared to giving BCG again in recurrent high-risk NMIBC after BCG treatment. CONCLUSIONS: Based on the findings of this review, gemcitabine may have a favorable impact on recurrence and progression-free survival than saline and mitomycin but we are uncertain about how major adverse events compare. The same is true when comparing gemcitabine to BCG in individuals with high-risk diseases who have previously failed BCG.