Sequence Therapy with FOLFIRINOX and Gemcitabine/Nab-Paclitaxel for Patients with Advanced Pancreatic Cancer – a Monocenter Retrospective Cohort Study

Author(s):  
Alexander Queck ◽  
Sharra Elango ◽  
Christine Koch ◽  
Dirk Walter ◽  
Jennifer Schmidt ◽  
...  

Background & aims: While irresectable pancreatic cancer has still a dismal overall prognosis, evidence about the optimal chemotherapy sequence is scarce. After treatment with FOLFIRINOX in first-line, Gemcitabine-monotherapy was established for years. As a potential treatment alternative after failure of FOLFIRINOX therapy, combination of Gemcitabine and Nab-Paclitaxel is used. However, this combination has formally not yet been approved for second-line treatment and investigation of efficiency and treatment tolerance is the aim of this trial. Methods: Therefore, we investigated 225 patients with histologically confirmed local advanced or metastatic pancreatic cancer in this retrospective mono-centre study (November 2010 – July 2019). Of this, 44 patients received FOLFIRINOX therapy and outcome was further analysed. The primary end point of this cohort was overall survival, secondary end points included progression free survival, response rate, and safety. Results: In most of the patients FOLFIRINOX as first-line treatment of irresectable pancreatic cancer resulted in temporary cancer control (partial response (PR): 50% and stable disease (SD): 18%), whereas tumor progression was observed in 23% of the patients. The median progression-free survival (PFS) time for FOLFIRINOX treatment was 7.3 months and median overall survival 10.3 months. Seven (16%) patients received additional local radio chemotherapy of the pancreatic tumor. During first-line therapy 8 (18%) patients had laparotomy for proof of resectability. Hereby, in three patients R0-, in three patients R1 resection, and irresectability in another 2 patients were achieved. Twenty-five of the 44 patients (57%) received second line therapy, namely 24 patients Gemcitabine/ Nab-Paclitaxel and 1 patient Gemcitabine and Erlotinib. Hereby, Gemcitabine/ Nab-Paclitaxel led again to temporary tumor control in 46% of the patients (PR: 21%, SD: 25%), while in 29% of the patient’s disease progression was observed. Corresponding median PFS for Gemcitabine and Nab-Paclitaxel treatment was 3.5 months. Patients who received second-line treatment with Nab-Paclitaxel and Gemcitabine had a more favorable prognosis (median OS: 17.4 versus 9.2 months; HR 0.32 [0.14 – 0.70], p<0.001) than patients who were not eligible for second-line treatment. Moreover, in multivariate analyses association with patients’ survival and tumor response to chemotherapy in both therapeutic lines and µGT below 100 IU/L in first-line FOLFIRINOX chemotherapy were observed. Conclusion: These real-world data suggest that Gemcitabine / Nab-Paclitaxel may be feasible after FOLFIRINOX therapy in patients with irresectable pancreatic cancer. However, prospective randomized data about the superiority to Gemcitabine monotherapy are needed.

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2744-2744 ◽  
Author(s):  
Ajay K Gopal ◽  
Brad S Kahl ◽  
Christopher Flowers ◽  
Peter Martin ◽  
Brian K Link ◽  
...  

Abstract Background: Follicular lymphoma (FL) is the most common indolent NHL with a heterogenous natural history of disease and a median survival of 8 to 12 y, albeit ranging between 1 to 20 y. Casulo et al. (2015) identified a high-risk FL cohort of patients with progression of disease (POD) at ≤24 months following initiation of immunochemotherapy with R-CHOP. Idelalisib (Zydelig) is a first-in-class, highly selective, oral inhibitor of PI3Kd which is indicated for relapsed FL or SLL following receipt of at least two lines of systemic chemotherapy. Retrospective subgroup analysis of the idelalisib registrational trial NCT01282424 (101-09) of a cohort with early POD following immunochemotherapy was performed to assess possible activity of idelalisib in this population. Methods: A subset of 46 patients enrolled in study 101-09 were identified as having been diagnosed with FL and having received first-line immunochemotherapy, of which 37 experienced early POD, defined as starting second-line treatment within 24 months of initial first-line treatment. For the latter group, descriptive statistics of demographic and baseline characteristics and inter-treatment intervals in months as well as Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) following initiation of immunochemotherapy and idelalisib were calculated. Population: Demographic characteristics of these 37 patients included median (range) age at initiation of idelalisib of 64 (33-84) y and 18 (48.6%) females. Histologic grade at diagnosis included 33 (89.2%) with grades 1 or 2 as well as 4 (10.8%) with grade 3A, while 21 (56.8%) patients had a FLIPI score ≥3. The mean (s.d.) number of prior therapies was 3.4±1.4, with a range of 2 to 8, while first-line therapies included 21 (56.8%) patients who received R-CHOP-based regimens, 7 (18.9%) who received BR, and 5 (13.5%) who received R-CVP. Mean (s.d.) inter-treatment intervals included 12.5±6.1 months between first- and second-line for all patients, 9.7±9.3 months between second- and third-line for all patients, 11.9±12.0 months between third- and fourth-line for 24 (64.9%) patients, and 11.8±7.6 months between fourth- and fifth-line for 15 (40.5%) patients. Median (range) time from first-line therapy to idelalisib initiation was 30.3 (8.9-94.7) months; no patient received idelalisib as second-line therapy. Results: Best responses included 5 (13.5%) patients with CR, 16 (43.2%) with PR, 2 (5.4%) with SD, and 1 (2.7%) with PD; median duration of response for those with CR or PR was 11.8 months (95% CI: 3.8 months, not evaluable). There were 7 (18.9%) deaths and 21 (56.8%) PFS events in this group. Estimated probabilities of survival (s.e.) and progression-free status at 2 y following initiation of idelalisib were 79%±7% and 29%±10%, respectively. Median PFS was 11.1 months (95% CI: 5.5, 19.3 months). Estimated probability of survival (s.e.) at 5 years following initiation of first-line treatment was 79%±8%. Median overall survival from both initiation of first-line immunochemotherapy as well as with idelalisib was not reached during the course of this study. Conclusions: Idelalisib may have significant clinical activity in high-risk and doubly-refractive FL following early relapse status post first-line immunochemotherapy. Given the small size of the studied subset population which may not be representative, further characterization in additional patients is warranted to ensure the generalizability of this finding, including consideration of further investigational protocols featuring targeted therapies employed both as single agents and in combination. Figure 1. Overall Survival From Initiation of First-line Treatment Figure 1. Overall Survival From Initiation of First-line Treatment Figure 2. Overall Survival From Initiation of Idelalisib Figure 2. Overall Survival From Initiation of Idelalisib Figure 3. Progression-Free Survival From Initiation of Idelalisib Figure 3. Progression-Free Survival From Initiation of Idelalisib Disclosures Gopal: Gilead, Spectrum, Pfizer, Janssen, Seattle Genetics: Consultancy; Spectrum, Pfizer, BioMarin, Cephalon/Teva, Emergent/Abbott. Gilead, Janssen., Merck, Milennium, Piramal, Seattle Genetics, Giogen Idec, BMS: Research Funding; Millennium, Seattle Genetics, Sanofi-Aventis: Honoraria. Kahl:Roche/Genentech: Consultancy; Seattle Genetics: Consultancy; Millennium: Consultancy; Cell Therapeutics: Consultancy; Celgene: Consultancy; Infinity: Consultancy; Pharmacyclics: Consultancy; Juno: Consultancy. Flowers:Infinity Pharmaceuticals: Research Funding; Genentech: Research Funding; Spectrum: Research Funding; Millennium/Takeda: Research Funding; Seattle Genetics: Consultancy; Spectrum: Research Funding; Pharmacyclics: Research Funding; AbbVie: Research Funding; AbbVie: Research Funding; Gilead Sciences: Research Funding; Pharmacyclics: Research Funding; Onyx Pharmaceuticals: Research Funding; Celegene: Other: Unpaid consultant, Research Funding; OptumRx: Consultancy; Gilead Sciences: Research Funding; Janssen: Research Funding; Acerta: Research Funding; Millennium/Takeda: Research Funding; Acerta: Research Funding; Infinity Pharmaceuticals: Research Funding; Janssen: Research Funding; Onyx Pharmaceuticals: Research Funding. Martin:Janssen: Consultancy, Honoraria; Acerta: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Bayer: Consultancy. Link:Genentech: Consultancy, Research Funding; Kite Pharma: Research Funding. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding. Ye:Gilead: Employment. Koh:Gilead: Employment. Abella:Gilead: Employment. Barr:Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Abbvie: Consultancy; Gilead: Consultancy. Salles:Calistoga Pharmaceuticals, Inc.; Celgene Corporation; Genentech, Inc.; Janssen Pharmaceutica Products, L.P.; Roche: Consultancy; Celgene Corporation; Roche and Gilead Sciences: Research Funding; Celgene Corporation; Roche: Speakers Bureau.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 496-496
Author(s):  
Yasumasa Takii ◽  
Kouichi Hurukawa ◽  
Satoshi Maruyama ◽  
Toshiyuki Yamazaki ◽  
Jun Nishimura ◽  
...  

496 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853-860) previously demonstrated the non-inferiority of Irinotecan plus S-1 (IRIS) to FOLFIRI for metastatic colorectal cancer (mCRC), with progression-free survival as the primary endpoint. IRIS plus bevacizumab (IRIS/Bev) was reported an active and generally well-tolerated first-line treatment for mCRC (Yuki et al. ASCO 2012 #3593). We planned a Phase II trial to evaluate the efficacy and safety of IRIS/Bev as second-line therapy for patients with mCRC. Methods: The study design was multicenter, single-arm, open-label phase II study. Eligible patients had to have mCRC with confirmed diagnosis of adenocarcinoma, history of oxaliplatin containing regimen as first-line therapy, an age from 20 to 80 years, ECOG performance status (PS) of 0-1. S-1 65 mg/m2 daily p.o. was given on days 1-14 and Irinotecan 75mg/m2 and Bevacizumab 10mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall response rate (OR), overall survival (OS), time to treatment failure (TTF) and safety. Results: From 08/12 until 11/06, 35 patients were enrolled. One patient did not start therapy. Thirty-four patients were investigated. Median age was 63 years (range, 38 to 82). Twenty-five patients were male. The mean of relative dose intensity of TS-1/Irinotecan/Bev were respectively 92.1%/87.0%/86.2%. The OR was 21.1% (7/33) and disease control rate was 84.8% (28/33). Median PFS was 9.3 months, median TTF was 8.2 month and median survival time 23.1 month. On safety analysis, the incidence of grade 3 or 4 adverse reactions were as follows: neutropenia, 14.7%; fatigue, 14.7%; white blood cell decreased, 11.8%; anorexia, 8.8%; anemia, 8.8%; diarrhea, 2.9%; proteinuria, 5.9%; thromboembolic event, 2.9%. Conclusions: IRIS/Bev is an active and well-tollarated second-line treatment for patients with mCRC. Clinical trial information: UMIN000001631.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 776-776
Author(s):  
Amisha Singh ◽  
Rachna T. Shroff ◽  
Ali McBride

776 Background: With an estimated six percent five-year survival, metastatic pancreatic adenocarcinoma is one of the most lethal cancers in the United States. Previously, treatments with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (G+A) have demonstrated improved overall survival versus gemcitabine alone. The purpose of this study is to compare institutional outcomes for the two regimens, FFX vs. G+A in metastatic pancreatic cancer. Methods: We conducted a retrospective review of medical records of all metastatic pancreatic cancer patients from 2010 to 2018 who received first line treatment with FFX or G+A at University of Arizona Cancer Center. Results: Thirty-five patients received combination treatment with G+A and 29 patients received FFX. Patient demographics: median age was 66 years in FFX vs 70 years in the G+A group; baseline CA-19-9 was 791 in FFX vs 738 in the G+A group. Median ECOG score was 1 for both groups. Median overall survival was 11.5 months in the FFX group (range 0-39 mos) vs 5 months in the G+A group (range 0-37 mos). Overall survival at 6 months was 75.9% vs 51.4% in FFX vs G+A groups respectively. Median progression-free survival was 6 months with FFX (range 0-25 mos) and 3 months with G+A (range 0-24 mos). Twenty-one of 29 patients in the FFX group pursued second line treatment, compared to 12 of 35 patients in the G+A group. Time to next treatment was 6 months in the FFX group vs 5 months in the G+A group. More adverse effects were noted with FFX, the most common being neuropathy and neutropenia, leading to treatment discontinuation due to adverse effects in 31% of patients, compared to 3% of patients in the G+A group. FFX patients required a higher median no. of office visits (35 visits vs 18 visits in the G+A group). Conclusions: FFX showed improved progression-free survival vs G+A; however, this could be due to more patients pursuing second line treatment in the FFX group. Compared to G+A, FFX patients had higher rates of treatment discontinuation due to adverse effects. FFX patients also required more office visits and further analysis is necessary to assess whether this resulted in poorer quality of life and increased total cost of care for patients treated with FFX.


2020 ◽  
Vol 12 ◽  
pp. 175883592094797
Author(s):  
Francesca Foschini ◽  
Fabiana Napolitano ◽  
Alberto Servetto ◽  
Roberta Marciano ◽  
Eleonora Mozzillo ◽  
...  

Background: Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death. In cases with metastasis, the combination of 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine-based chemotherapy regimens are considered the standard of care. However, the optimal sequence of these regimens is unclear. Methods: This retrospective study initially evaluated 186 patients with locally advanced/metastatic pancreatic cancer at three Italian institutions between February 2013 and October 2019. All patients had progressed after receiving gemcitabine-based first-line chemotherapy and were subsequently offered second-line FOLFIRINOX, FOLFOX-6, or FOLFIRI treatment. This study evaluated progression-free survival (PFS), overall survival from the start of second-line treatment (OS2), overall survival from the start of first-line treatment (OS1), and safety outcomes. Results: A total of 77 patients received ⩾4 cycles of second-line chemotherapy and were considered eligible: 15 patients received FOLFIRINOX, 32 patients received FOLFOX-6, and 30 patients received FOLFIRI. The FOLFIRINOX group had median PFS of 26.29 weeks and median OS2 of 47.86 weeks, while the FOLFIRI group had median PFS of 10.57 weeks and median OS2 of 25.00 weeks ( p = 0.038). No significant differences were observed between the FOLFIRINOX and FOLFOX-6 groups in terms of PFS (26.29 weeks versus 23.07 weeks) or OS2 (47.86 weeks versus 42.00 weeks). The most common grade 3–4 toxicities were anemia, neutropenia, and thrombocytopenia, which occurred more frequently in the FOLFIRINOX and FOLFOX-6 groups. Conclusion: Relative to the FOLFIRI regimen, the FOLFIRINOX regimen had a favorable toxicity profile and better survival outcomes. No significant differences were observed relative to the FOLFOX-6 regimen.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0248922
Author(s):  
Calin Cainap ◽  
Rodica Ana Ungur ◽  
Ovidiu-Vasile Bochis ◽  
Patriciu Achimas ◽  
Catalin Vlad ◽  
...  

Colorectal cancer remains one of the most frequent malignancies (third place at both genders) worldwide in the last decade, owing to significant changes in modern dietary habits. Approximately half of the patients develop metastases during the course of their disease. The available therapeutic armamentarium is constantly evolving, raising questions regarding the best approach for improving survival. Bevacizumab remains one of the most widely used therapies for treating metastatic colorectal cancer and can be used after progression. This study aimed to identify the best chemotherapy partner for bevacizumab after progression. We performed a retrospective analysis of patients with metastatic colorectal cancer who were treated with bevacizumab as first- and second-line chemotherapy. Data were collected for 151 patients, 40 of whom were treated with double-dose bevacizumab after the first progression. The two standard chemotherapy regimens combined with bevacizumab were FOLFIRI/CAPIRI and FOLFOX4/CAPEOX. The initiation of first-line treatment with irinotecan-based chemotherapy improved progression-free survival and time to treatment failure but not overall survival. After the first progression, retreatment with the same regimen as that used in the induction phase was the best approach for improving overall survival (median overall survival: 46.5 vs. 27.0 months for the same vs. switched strategy, respectively). No correlations were observed between the dose intensity of irinotecan, oxaliplatin, 5-fluorouracil, or bevacizumab and the overall survival, progression-free survival in the first-/second-line treatment, and time to treatment failure. Interaction between an irinotecan-based regimen as a second-line treatment and double-dose bevacizumab after progression was associated with an improved overall survival (p = 0.06). Initiating systemic treatment with an irinotecan-based regimen in combination with bevacizumab improved the progression-free survival in the first-line treatment and time to treatment failure. In terms of overall survival, bevacizumab treatment after the first progression is better partnered with the same regimen as that used in the induction phase.


Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Kotone Hayuka ◽  
Hiroyuki Okuyama ◽  
Akitsu Murakami ◽  
Yoshihiro Okita ◽  
Takamasa Nishiuchi ◽  
...  

<b><i>Introduction:</i></b> Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. <b><i>Methods:</i></b> Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. <b><i>Results:</i></b> The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). <b><i>Conclusions:</i></b> GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15586-e15586
Author(s):  
Mohamed Alghamdi ◽  
Shouki Bazarbashi ◽  
Elsamany Shereef ◽  
Mervat Mahrous ◽  
Omar Al shaer ◽  
...  

e15586 Background: In Saudi Arabia, the incidence of colorectal cancer has been increased over the past few years. The optimal treatment beyond the second line is not fully understood. To the best of our knowledge, the efficacy and disease outcomes of triflurodine/tipiracil in Saudi patients with refractory metastatic colorectal cancer(mCRC) has not been studied yet. Our study is a real-life practice evaluation of the efficacy of triflurodine/tipiracil in patients with refractory mCRC. Moreover, the prognosis and the prognostic significance of the different clinical variables have been analyzed. Methods: A retrospective, multi-centers ( 5 centers representative of Saudi Arabia )observational study in patients with mCRC who have received triflurodine/tipiracil beyond oxaliplatin & Irinotecan-based chemotherapy between December 2018-December 2020.We aimed to assess the response to triflurodine/tipiracil, to evaluate the progression-free survival (PFS ), the overall survival (OS), and the associated factors of prognostic significance. Results:The data of 100 patients with refractory mCRC who has received triflurodine/tipiracil have been analyzed. The mean age was 55.2 +11.8 years. Forty-two patients were (42%) females and 58 (58%) were male patients. Sigmoid was the most common primary site of cancer in 35 (35%) patients, followed by rectum 29 (29%). Peritoneal metastasis was present in 17 (23.3%) patients ,liver in 51(56.6%) and lung in 39 (50.7%). Metastatic sites were ≥ 2 in 45 (45%) patients. Metastatic lesions were ≥ 5 in 65 (65%) patients. Xelox chemotherapy regimen was the most commonly used first-line chemotherapy which represents 43%, while Folfiri or Xeliri combination was the most used second line in 57 (60%). For the third line, Folfox or Xelox was used in 81 (83.5%) patients. The fourth line was given to 49 (67.1%). For first-line biological agents, Cetuximab was used most frequently 31 (46.3%).Evaluation of the response to treatment with triflurodine/tipiracil revealed one patient (1%) with a complete response,3 patients (3%) with partial response, 28 (28%) patients with stable disease, and 66 (66%) showed progressive disease. The estimated median progression-free survival was 5 months ( 3.839 - 6.161) and the median overall survival was 12 months (9.732-14.268). The log-rank analysis showed that the baseline neutrophils ≤ 75 % ( P-value= 0.0092) and low hemoglobin level (P-value= 0.0245) were strongly associated with a higher survival. By multivariate Cox regression analysis, the neutrophil count ≤ 75 % was the only independent predictor for survival. Conclusions: Trifluridine/tipiracil is effective in patients with refractory mCRC. The low neutrophil count might predict a better overall survival.


Author(s):  
Mikifumi Koura ◽  
Masaki Shiota ◽  
Shohei Ueda ◽  
Takashi Matsumoto ◽  
Satoshi Kobayashi ◽  
...  

Abstract Objective This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). Methods The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. Results In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40–0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. Conclusions This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.


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