scholarly journals Cladribine tablets added to IFN-β in active relapsing MS

2018 ◽  
Vol 5 (5) ◽  
pp. e477 ◽  
Author(s):  
Xavier Montalban ◽  
Thomas P. Leist ◽  
Bruce A. Cohen ◽  
Harold Moses ◽  
Jackie Campbell ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Lymphocyte Count ◽  
Phase Ii Study ◽  
Clinical Trial Registration ◽  
Safety And Efficacy ◽  
Treatment Groups ◽  
Grade 3 ◽  
To Receive

ObjectiveTo evaluate the safety and efficacy of cladribine tablets in patients still experiencing active relapsing MS despite interferon (IFN)-β treatment.MethodsA 96-week phase II study, randomizing patients treated with IFN-β to cladribine tablets 3.5 mg/kg/IFN-β or placebo/IFN-β. Patients were to receive cladribine tablets 3.5 mg/kg/IFN-β or placebo/IFN-β in a 2:1 ratio (n = 172) with safety and exploratory efficacy outcomes being assessed.ResultsAdverse events (AEs) and serious AEs were similar across treatment groups, except lymphopenia. Fifty of 124 (40.3%) cladribine/IFN-β recipients vs 0% of placebo/IFN-β recipients reported lymphopenia as an AE, with grade 3/4 lymphopenia (laboratory lymphocyte count < 500 cells/mm3) experienced by 79/124 (63.7%) vs 1 (2.1%), respectively. Patients treated with cladribine tablets 3.5 mg/kg/IFN-β were 63% less likely to have a qualifying relapse than placebo/IFN-β recipients, and cladribine tablets 3.5 mg/kg/IFN-β reduced most MRI measures of disease activity.ConclusionsIn patients with active relapsing MS despite IFN-β treatment, cladribine tablets 3.5 mg/kg/IFN-β reduced relapses and MRI lesion activity over 96 weeks compared with placebo/IFN-β but led to an increased incidence of lymphopenia.Classification of evidenceThis study provides Class I evidence that for patients with active relapsing MS despite IFN-β treatment, cladribine tablets added to IFN-β reduced relapses and MRI lesion activity over 96 weeks and increased the incidence of lymphopenia.Clinical trial registrationNCT00436826.

Safety and efficacy outcomes with nivolumab plus ipilimumab in patients with advanced renal cell carcinoma and low Karnofsky performance status: Results from the CheckMate 920 trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 315-315
Author(s):  
Thomas E. Hutson ◽  
Bradley Curtis Carthon ◽  
Jeffrey Yorio ◽  
Sunil Babu ◽  
Heidi Ann McKean ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Safety And Efficacy ◽  
Grade 3

315 Background: Combination therapy with nivolumab + ipilimumab (NIVO+IPI) has demonstrated long-term efficacy and tolerability for patients (pts) with previously untreated advanced renal cell carcinoma (aRCC). Most pivotal clinical trials in pts with aRCC have excluded pts with low Karnofsky performance status (KPS; < 70%). CheckMate 920 is a multi-arm, phase IIIb/IV, open-label clinical trial of NIVO+IPI treatment in pts enrolled in a community practice setting with aRCC and a high unmet medical need. We present safety and efficacy results for the cohort of pts with aRCC of any histology and KPS 50%–60% from CheckMate 920 (NCT02982954). Methods: Pts with previously untreated advanced/metastatic RCC and KPS 50%–60% received NIVO 3 mg/kg + IPI 1 mg/kg Q3W × 4 doses followed by 480 mg NIVO Q4W for ≤ 2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥ 3 immune-mediated adverse events (imAEs) within 100 days of last dose of study drug. Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 (both per investigator). Exploratory endpoints included overall survival (OS). Results: Of 25 treated pts with KPS 50%–60%, 76% were men; median age was 67 years (range, 34–81). IMDC risk was favorable in 0%, intermediate in 32%, and poor in 68% of pts; 84% had clear cell and 16% had non-clear cell RCC histology. With a minimum follow-up of 25 months, median duration of therapy (95% CI) was 2.3 months (2.1–7.7) for NIVO and 2.1 months (2.1–2.1) for IPI. The median number of doses (range) received was 4 (1–27) for NIVO and 4 (1–4) for IPI; 76% of pts received ≥ 4 NIVO doses and 68% received all 4 IPI doses. The only grade 3–4 imAEs by category were hepatitis (4.0%) and adrenal insufficiency (4.0%). No grade 5 imAEs occurred. Overall, 4 (16%) pts discontinued due to any-grade adverse events (n = 1 each for elevated AST, malignant neoplasm progression, back pain, and acetabulum fracture). Of 18 evaluable pts, ORR was 33.3% (95% CI, 13.3–59.0); no pts had a complete response and 6 had partial response. Median time to objective response was 4.5 months (range, 2.5–24.7). Median duration of objective response was 20.6 months (range, 0.03+–24.2+). Median PFS was 4.6 months (95% CI, 2.5–14.8). Median OS was 15.6 months (95% CI, 5.3–25.1). Conclusions: NIVO+IPI demonstrated an acceptable safety profile and promising antitumor activity in pts with previously untreated aRCC and KPS 50%–60%. The combination was tolerated at a dose intensity similar to that observed in clinical trials conducted in pts with higher KPS (≥ 70%). These data support the value of NIVO+IPI in pts who may not be considered ideal candidates for this therapy and consequently may have limited treatment options. Clinical trial information: NCT02982954 .

scholarly journals P722 Upadacitinib was not associated with anaemia in patients with moderately to severely active ulcerative colitis: Results from the U-ACHIEVE study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S580-S582
Author(s):  
G D’Haens ◽  
X Hebuterne ◽  
P D R Higgins ◽  
E V Loftus- ◽  
W Zhou ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Janus Kinase ◽  
Double Blind ◽  
Once Daily ◽  
Treatment Groups ◽  
The Common ◽  
Grade 3 ◽  
To Receive ◽  
Dose Dependent

Abstract Background Anaemia is a frequent complication in patients with Crohn’s disease and ulcerative colitis (UC), and patients who respond to treatment generally show improvement in anaemia. Decrease in haemoglobin (Hgb) levels and anaemia may be associated with Janus kinase (JAK) inhibitors. Upadacitinib (UPA), an oral JAK1 selective inhibitor, has demonstrated favourable dose-dependent efficacy in patients with moderately to severely active UC.1 This analysis of data from the U-ACHIEVE study addressed effects of UPA treatment on Hgb levels in patients with UC. Methods U-ACHIEVE (NCT02819635) was a randomised, double-blind, placebo (PBO)-controlled phase 2b clinical trial. Adults with moderately to severely active UC were randomised to receive 7.5, 15, 30, or 45 mg UPA or PBO once daily (QD) for 8 weeks. Hgb levels were measured for all groups at baseline (BL) and weeks 2, 4, 6, and 8. Mean change from BL was calculated for each group. p-values for comparison between UPA and PBO groups were calculated using one-way ANOVA; no multiplicity adjustment was applied. Percentage of patients with Hgb values grade 2 (15–20 g/l Hgb decrease from BL), grade 3 (&lt;80 g/l Hgb level or 21–29 g/l Hgb decrease from BL), and grade 4 (&lt;70 g/l Hgb level or &gt;29 g/l Hgb decrease BL) anaemia were determined for all treatment groups using the Common Terminology Criteria for Adverse Events version 5. Adverse events (AE) were reported by investigators. Results Included in the analysis were 250 patients (mean age ± SD, 42.3 ± 14.2 years; disease duration, 8.2 ± 2.5 years). At BL, most treatment groups had similar mean Hgb levels, except for the 15 mg UPA group, which had significantly lower Hgb levels vs. PBO group (Table). Increased or stable mean levels of Hgb at week 8 vs. BL were observed in most UPA treatment groups. The PBO group had the greatest decrease in Hgb vs. BL at week 8 compared with UPA treatment groups (Figure). Grade ≥2 anaemia was reported in 17.4% of patients receiving PBO and 14.4% of all patients receiving UPA (14.9%, 12.2%, 12.0%, and 17.9% of patients receiving 7.5, 15, 30, and 45 mg UPA, respectively). Grade ≥3 anaemia was reported in 8.7% of patients receiving PBO and 5% of all patients receiving UPA (6.4%, 6.1%, 6.0%, and 1.8% of patients receiving 7.5, 15, 30, and 45 mg UPA, respectively). One subject receiving 7.5 mg QD UPA had grade 4 anaemia. AE of anaemia was reported in 6.5% of patients receiving PBO and in 2.1%, 8.2%, and 3.8% of patients receiving 7.5, 15, and 30 mg UPA, respectively, but not in the 45 mg UPA group. Conclusion Decreased Hgb levels over time were observed more frequently in the PBO group. The maintenance of Hgb levels in patients receiving UPA was likely because of improvement of underlying UC. Reference

scholarly journals A Phase II Trial of the Double Epigenetic Priming Regimen Including Chidamide and Decitabine for Relapsed/Refractory Acute Myeloid Leukemia

2021 ◽  
Vol 11 ◽  
Author(s):  
Jia Yin ◽  
Chao-Ling Wan ◽  
Ling Zhang ◽  
Hao Zhang ◽  
Lian Bai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Acute Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
Clinical Trial Registration ◽  
Idh Mutations ◽  
Refractory Acute Myeloid Leukemia ◽  
Grade 3 ◽  
Acute Myeloid

ObjectiveTo explore the role of chidamide, decitabine plus priming regimen in the salvage treatment of relapsed/refractory acute myeloid leukemia.MethodsA clinical trial was conducted in relapsed/refractory acute myeloid leukemia patients using chidamide, decitabine, cytarabine, idarubicin, and granulocyte-colony stimulating factor, termed CDIAG, a double epigenetic priming regimen.ResultsThirty-five patients were recruited. Three patients received 2 treatment cycles. In 32 evaluable patients and 35 treatment courses, the completed remission rate (CRR) was 42.9%. The median OS time was 11.7 months. The median OS times of responders were 18.4 months, while those of nonresponders were 7.4 months (P = 0.015). The presence of RUNX1 mutations was associated with a high CRR but a short 2-year OS (P = 0.023) and PFS (P = 0.018) due to relapse after treatment. The presence of IDH mutations had no effect on the remission rate (80.0% vs. 73.3%), but showed a better OS (2-year OS rate: 100.0% vs. 28.9%). Grade 3/4 nonhematological adverse events included pneumonia, hematosepsis, febrile neutropenia, skin and soft tissue infection and others.ConclusionThe double epigenetic priming regimen (CDIAG regimen) showed considerably good antileukemia activity in these patients. Adverse events were acceptable according to previous experience. The study was registered as a clinical trial.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier:NCT03985007

scholarly journals A Randomized Phase 2 Study of ADXS11-001 Listeria monocytogenes–Listeriolysin O Immunotherapy With or Without Cisplatin in Treatment of Advanced Cervical Cancer

2018 ◽  
Vol 28 (4) ◽  
pp. 764-772 ◽  
Author(s):  
Partha Basu ◽  
Ajay Mehta ◽  
Minish Jain ◽  
Sudeep Gupta ◽  
Rajnish V. Nagarkar ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Listeria Monocytogenes ◽  
Adverse Events ◽  
Progression Free Survival ◽  
Combination Group ◽  
Listeriolysin O ◽  
Phase 2 ◽  
Safety And Efficacy ◽  
Treatment Groups ◽  
Phase 2 Study

ObjectivesA global unmet medical need exists for effective treatments for persistent, recurrent, or metastatic cervical cancer, as patients have a short life expectancy. Recently, immunotherapies have shown promising survival benefits for patients with advanced forms of cancer. Axalimogene filolisbac (ADXS11-001), aListeria monocytogenesimmunotherapy with a broad effect on the immune system, is under investigation for treatment of human papillomavirus–associated cancers including cervical cancer.MethodsThis phase 2 study evaluated the safety and efficacy of ADXS11-001, administered with or without cisplatin, in patients with recurrent/refractory cervical cancer following prior chemotherapy and/or radiotherapy. A total of 109 patients were treated, and 69 were evaluable for tumor response at equal to or more than 3 months postbaseline.ResultsMedian overall survival (OS) was comparable between treatment groups (ADXS11-001: 8.28 months; 95% confidence interval [CI], 5.85–10.5 months; ADXS11-001 + cisplatin: 8.78 months; 95% CI, 7.4–13.3 months). The 12- and 18-month milestone OS rates were 30.9% versus 38.9%, and 23.6% versus 25.9% for each group, respectively (34.9% and 24.8% combined). Median progression-free survival (6.10 vs 6.08 months) and the overall response rate (17.1% vs 14.7%) were similar for both groups. ADXS11-001 was generally well tolerated; adverse events were predominantly mild to moderate in severity and not related to treatment. More adverse events were reported in the combination group (429 vs 275).ConclusionsThese promising safety and efficacy results, including the encouraging 12-month 34.9% combined OS rate, warrant further investigation of ADXS11-001 for treatment of recurrent/refractory cervical cancer.

Retrospective Review of Safety and Efficacy of Anlotinib in Advanced Osteosarcoma With Metastases After Failure of Standard Multimodal Therapy

2021 ◽  
Author(s):  
Hanqing Li ◽  
Yang Li ◽  
Lei Song ◽  
Qiuchi Ai ◽  
shuai zhang
Keyword(s):  
Adverse Events ◽  
Multimodal Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Common Drug ◽  
Grade 3 ◽  
Therapeutic Doses

Abstract To study and observe the safety and efficacy of anlotinib in the treatment of advanced osteosarcoma with metastases. We retrospectively studied patients with advanced osteosarcoma and metastases who received anlotinib treatment in our hospital from June 2018 to April 2020. All patients had received standard multimodal therapies, before taking anlotinib. Therapeutic doses of anlotinib were 12 mg for adults and 10 mg for children and adolescents once a day for 2 consecutive weeks, followed by a week of withdrawal. This 3-week cycle of treatment was continued until the tumor progressed rapidly or the patients failed to tolerate the side effects. Adverse drug reactions were recorded, and therapeutic efficacy was evaluated based on progression free survival (PFS), disease control rate (DCR), overall survival (OS), and objective response rate (ORR). The median PFS was 9.81 ± 0.9 months, and the 6-month and 10-month PFS rates were 73.3% and 33.3%, respectively. The median OS was 11.43 ± 0.58 months. No patients achieved complete response. After 6 months of treatment, the DCR and ORR were 80% and 13.3%, respectively. No drug-related deaths or Grade 4 adverse events occurred in the patients. Five patients (33.3%) had Grade 3 adverse events. The most common drug-related adverse events were hand-food syndrome, fatigue, high blood pressure, anorexia, and pneumothorax. Anlotinib had a certain curative effect on patients with advanced osteosarcoma and metastases after failure of standard treatment. The adverse events were mostly tolerable or relieved after treatment.

scholarly journals Sorafenib treatment by Child–Pugh score in Latin American patients with hepatocellular carcinoma

2020 ◽  
Vol 16 (31) ◽  
pp. 2511-2520
Author(s):  
Laura L de Guevara ◽  
Lucy Dagher ◽  
Vanessa MV Arruda ◽  
Keiko Nakajima ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Latin American ◽  
Treatment Option ◽  
Real World ◽  
Safety Profile ◽  
Treatment Duration ◽  
Sorafenib Treatment ◽  
Safety And Efficacy ◽  
Grade 3

Aim: To evaluate sorafenib treatment in Latin American patients with unresectable hepatocellular carcinoma in the real-world GIDEON study. Patients & methods: Sorafenib administration, safety and efficacy were analyzed by Child–Pugh status. Results: Of 90 evaluable patients (37% Child–Pugh A, 46% Child–Pugh B and 3% Child–Pugh C at study entry), 97% started sorafenib at 800 mg/day. Patients with Child–Pugh B7 had the longest median treatment duration of sorafenib (33.1 weeks). Sorafenib-related adverse events occurred in 58% of patients with Child–Pugh A (21% grade 3/4) and 46% with Child–Pugh B (7% grade 3/4). Conclusion: Sorafenib had a similar safety profile across patients with Child–Pugh A and B and is a treatment option for both groups.

scholarly journals Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART

2019 ◽  
Vol 74 (9) ◽  
pp. 2707-2715 ◽  
Author(s):  
Holly E Rawizza ◽  
Kristin M Darin ◽  
Regina Oladokun ◽  
Biobele Brown ◽  
Babatunde Ogunbosi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Treatment Options ◽  
Severe Neutropenia ◽  
Laboratory Monitoring ◽  
Safety And Efficacy ◽  
Cell Percentage ◽  
Grade 3 ◽  
Cd4 Cell

Abstract Background TB is the leading cause of death among HIV-infected children, yet treatment options for those who require PI-based ART are suboptimal. Rifabutin is the preferred rifamycin for adults on PI-based ART; only one study has evaluated its use among children on PIs and two of six children developed treatment-limiting neutropenia. Methods Since 2009, rifabutin has been available for HIV/TB-coinfected children requiring PI-based ART in the Harvard/APIN programme in Nigeria. We retrospectively analysed laboratory and clinical toxicities at baseline and during rifabutin therapy, and examined HIV/TB outcomes. Results Between 2009 and 2015, 48 children received rifabutin-containing TB therapy with PI (lopinavir/ritonavir)-based ART: 50% were female with a median (IQR) baseline age of 1.7 (0.9–5.0) years and a median (IQR) CD4+ cell percentage of 15% (9%–25%); 52% were ART experienced. Eighty-five percent completed the 6 month rifabutin course with resolution of TB symptoms and 79% were retained in care at 12 months. Adverse events (grade 1–4) were more common at baseline (27%) than during rifabutin treatment (15%) (P = 0.006). Absolute neutrophil count was lower during rifabutin compared with baseline (median = 1762 versus 2976 cells/mm3, respectively), but only one instance (2%) of grade 3 neutropenia occurred during rifabutin treatment. Conclusions With clinical and laboratory monitoring, our data suggest that rifabutin is a safe option for TB therapy among children on PI-based ART. By contrast with the only other study of this combination in children, severe neutropenia was rare. Furthermore, outcomes from this cohort suggest that rifabutin is effective, and a novel option for children who require PI-based ART. Additional study of rifabutin plus PIs in children is urgently needed.

scholarly journals Transnasal Humidified Rapid Insufflation Ventilatory Exchange With Nasopharyngeal Airway Facilitates Apneic Oxygenation: A Randomized Clinical Noninferiority Trial

2020 ◽  
Vol 7 ◽  
Author(s):  
Lingke Chen ◽  
Liu Yang ◽  
Weitian Tian ◽  
Xiao Zhang ◽  
Yanhua Zhao ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Lower Boundary ◽  
Clinical Trial Registration ◽  
Apneic Oxygenation ◽  
Nasopharyngeal Airway ◽  
Airway Opening ◽  
The Difference ◽  
To Receive ◽  
Noninferiority Margin ◽  
Upper Boundary

Background: Transnasal humidified rapid insufflation ventilatory exchange (THRIVE) was used to extend the safe apnea time. However, THRIVE is only effective in patients with airway opening. Nasopharyngeal airway (NPA) is a simple device that can help to keep airway opening. This study aimed to investigate the noninferiority of NPA to jaw thrust for airway opening during anesthesia-induced apnea.Methods: This was a prospective randomized single-blinded noninferiority clinical trial on the use of THRIVE in patients with anesthesia-induced apnea. The participants were randomly allocated to receive NPA or jaw thrust. The primary outcomes were PaO2 and PaCO2 at 20 min after apnea, with noninferiority margin criteria of −6.67 and 0.67 kPa, respectively.Results: A total of 123 patients completed the trial: 61 in the NPA group and 62 in the jaw thrust group. PaO2 at 20 min after apnea was 42.9 ± 14.0 kPa in the NPA group and 42.7 ± 13.6 kPa in the jaw thrust group. The difference between these two means was 0.25 kPa (95% CI, −3.87 to 4.37 kPa). Since the lower boundary of the 95% CI was &gt; −6.67 kPa, noninferiority was established because higher PO2 is better. PaCO2 at 20 min after apnea was 10.74 ± 1.09 kPa in the NPA group and 10.54 ± 1.18 kPa in the jaw thrust group. The difference between the two means was 0.19 kPa (95% CI, −0.14 to 0.53 kPa). Since the upper boundary of the 95% CI was &lt;0.67 kPa, noninferiority was established because lower PCO2 is better. No patient had a SpO2 &lt; 90% during apnea.Conclusion: When THRIVE was applied during anesthesia-induced apnea, NPA placement kept airway opening and was noninferior to jaw thrust in terms of its effects on PaO2 and PaCO2 at 20 min after apnea.Clinical Trial Registration:ClinicalTrials.gov (NCT03741998).

scholarly journals Real-world adverse events with niraparib 200 mg/day maintenance therapy in ovarian cancer: a retrospective study

2019 ◽  
Vol 15 (36) ◽  
pp. 4197-4206
Author(s):  
Jack R Gallagher ◽  
Kylee Jean Heap ◽  
Susan Carroll ◽  
Karin Travers ◽  
Brooke Harrow ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Retrospective Study ◽  
Adverse Events ◽  
Real World ◽  
Recurrent Ovarian Cancer ◽  
Medical Record Data ◽  
Platinum Based Chemotherapy ◽  
Record Data ◽  
Grade 3

Aim: To assess real-world occurrence of common clinical trial-reported adverse events (AE) among patients with recurrent ovarian cancer initiating niraparib 200 mg/day. Materials & methods: This retrospective observational study used physician-extracted anonymized medical record data of eligible patients initiating niraparib 200 mg/day after platinum-based chemotherapy. Results: Of 153 patients, 57 (37%) experienced ≥1 of the three most common all-grade AEs within 3 months after niraparib initiation: nausea (16%; grade 3/4: 2%), thrombocytopenia (14%; grade 3/4: 3%) and fatigue (24%; grade 3/4: 3%). In the ENGOT-OV16/NOVA trial, these respective AEs occurred in 74, 61 and 59% of patients. Conclusion: Incidence of common clinical trial-reported AEs was lower among patients initiating niraparib 200 mg/day in real-world practice versus patients initiating niraparib 300 mg/day in ENGOT-OV16/NOVA.

scholarly journals Efficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: an open-label, single arm, phase 2 trial

2020 ◽  
Vol 122 (5) ◽  
pp. 634-639 ◽  
Author(s):  
Ali Belkouz ◽  
Judith de Vos-Geelen ◽  
Ron A. A. Mathôt ◽  
Ferry A. L. M. Eskens ◽  
Thomas M. van Gulik ◽  
...  
Keyword(s):  
Adverse Events ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Salvage Treatment ◽  
Phase 2 ◽  
Serious Adverse Events ◽  
Clinical Trial Registration ◽  
Tract Cancer ◽  
Grade 3

Abstract Background No standard treatment is available for advanced biliary tract cancer (BTC) after first-line therapy with gemcitabine plus cisplatin (GEMCIS). The objective of this study was to evaluate safety and anti-tumour activity of fluorouracil, leucovorin, irinotecan plus oxaliplatin (FOLFIRINOX) as salvage treatment in patients with previously treated advanced BTC. Methods In this two-stage phase 2 study, patients with advanced BTC who had disease progression or unacceptable toxicity after ≥3 cycles of GEMCIS were eligible. Primary endpoints were safety and efficacy (defined as objective response rate, ORR). In stage one, ten patients were treated with FOLFIRINOX every 2 weeks. In stage two, an additional 20 patients were enrolled at a starting dose as defined in stage one, provided that in stage ≥1 objective response or ≥2 stable diseases were observed and ≤3 patients had serious adverse events (SAEs) within the first 6 weeks of treatment. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results Forty patients were screened for eligibility and 30 patients were enrolled. In stage one, one patient had a partial response and five patients had stable disease. One patient had a SAE during the first 6 weeks of treatment, and five patients required a dose reduction due to adverse events. The most common grade 3–4 adverse events in stage one were neutropaenia, mucositis and diarrhoea. Stage two was initiated with FOLFIRINOX in an adapted dose. In stage two, grade 3–4 neutropaenia, diarrhoea, nausea and vomiting were the most common adverse events. The ORR, median PFS and OS in all patients were 10%, 6.2 and 10.7 months, respectively. Conclusions In patients with advanced BTC who progressed after or were intolerant to GEMCIS, FOLFIRINOX can be administered safely and could be considered as an option for salvage treatment in these patients. Clinical trial registration ClinicalTrials.gov Identifier NCT02456714.

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