Single-institution experience with FOLFIRINOX in advanced pancreatic cancer (PC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 330-330 ◽  
Author(s):  
Krishna Soujanya Gunturu ◽  
Jaykumar Ranchodbhai Thumar ◽  
Howard S. Hochster ◽  
Stacey Stein ◽  
Xiaopan Yao ◽  
...  
Keyword(s):  
Historical Data ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Cancer Center ◽  
Clinically Significant ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
The Impact ◽  
Dose Reductions

330 Background: FOLFIRINOX provides clinically significant benefit in advanced PC compared to gemcitabine (Conroy et al. New Engl J Med 2011;364:1817). Despite superior efficacy, toxicities have tempered enthusiasm for FOLFIRINOX and limited its use in full doses. To assess the impact of dose attenuations on toxicity and efficacy, we reviewed our experience with FOLFIRINOX in pts with advanced PC. Methods: We performed a retrospective review of dose, toxicity, efficacy of FOLFIRINOX in all pts with locally advanced unresectable PC (LAPC) and metastatic PC (MPC) treated with FOLFIRINOX at Yale Cancer Center between 06/10 and 06/11. Dose attenuations were at the treating physician’s discretion. All pts received prophylactic pegfilgrastim. Pts were treated until progression, unacceptable toxicity, or surgical resection. Toxicities and efficacy were compared to historical data reported by Conroy. Results: 31 pts with ECOG PS 0 or 1 were treated. Pt characteristics: LAPC 15; MPC 16; median (med) age 60 yrs (range 48-78); male 11; prior chemotherapy 5 (adjuvant 3). Med number of cycles received was 6 (range 1-18). Only 5 pts received full doses of all drugs with cycle 1. Dose reductions with cycle 1 were: IRI 26 pts, OX 10 pts, bFU 10 pts, infusional FU 1 pt. b5FU was omitted in 6 pts. Med relative dose intensities were: OX 88%, IRI 64%, b-FU 57%, infusional FU 100% (compared to OX 78%, IRI 81%, and FU 82% [Conroy]). The % of pts with grade 3 or 4 toxicities was: fatigue or mucositis, 9.6%; dehydration or neutropenia 6.4%; vomiting, thromboembolism, febrile neutropenia, thrombopenia or anemia, 3.2%. Neutropenia (p<0.0001), diarrhea (p<0.03), fatigue (p<0.02) were significantly decreased compared to historical data (Conroy). Response (CR+PR) in 30 evaluable pts was 33% (1 CR, 9 PR, 14 SD, 6 PD) and similar to historical data (31.6%; p 0.21). 2 pts with LAPC underwent resection. Evaluation for OS and PFS is ongoing. Conclusions: Our findings suggest that dose attentuation of FOLFIRINOX, esp IRI and bFU, with prophylactic pegfilgrastim is associated with improved tolerability and equivalent response rate compared to full dose FOLFIRINOX in advanced PC. The impact of dose attenuations on toxicity and efficacy warrants further evaluation in both LAPC and MPC.

Single institution experience with FOLFIRINOX in advanced pancreatic cancer (PC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14534-e14534
Author(s):  
Krishna Soujanya Gunturu ◽  
Jaykumar Ranchodbhai Thumar ◽  
Howard S. Hochster ◽  
Stacey Stein ◽  
Xiaopan Yao ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Cancer Center ◽  
Control Group ◽  
Kaplan Meier ◽  
Sample Proportion ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
The Impact

e14534 Background: FOLFIRINOX significantly increases survival in metastatic PC compared to gemcitabine (Conroy. New Engl J Med 2011;364). Despite superior efficacy, toxicities have tempered enthusiasm for FOLFIRINOX in full doses. To assess the impact of dose attenuations on toxicity and efficacy, we reviewed our experience with FOLFIRINOX in advanced PC pts. Methods: We performed a retrospective review of dose, toxicity, and efficacy of FOLFIRINOX in all pts with locally advanced unresectable PC (LAPC) and metastatic PC (MPC) treated with FOLFIRINOX at Yale Cancer Center between 06/10 and 07/11. Dose attenuations were at the treating physician’s discretion. All pts received prophylactic pegfilgrastim. Pts were treated until progression, unacceptable toxicity, or surgical resection. Toxicities and RR were compared to Conroy’s data using one sample proportion test. Overall survival (OS) and progress free survival (PFS) were estimated by Kaplan-Meier method. Results: 35 pts with ECOG PS 0/1 were treated. Pt characteristics: LAPC 16; MPC 19; median age 61 yrs (range 48-77); male 13; prior chemotherapy 5. Median (med) number of cycles was 10 (range 1-26). FOLFIRINOX was dose attenuated with the first cycle in 29 pts: IRI reduced in 27 and omitted in 1, OX reduced in 10, bFU reduced in 9 and omitted in 7, LV decreased in 11, FU infusion reduced in 3. Med doses of OX, IRI, bFU, and infusion FU were 90%, 68%, 68%, and 100%, respectively, compared to 78%, 81%, 82%, and 82%, respectively, in Conroy’s FOFIRINOX arm (control). We are following pts for PFS and OS. RRs were 50% and 47% in pts with LAPC and MPC. RR in MPC didnot differ significantly from the control (p=0.19). We observed significantly less grade 3/4 fatigue (p=0.008) and neutropenia (p<0.0001) compared to the control group. Conclusions: Our findings suggest that dose attenuation of FOLFIRINOX, esp IRI and bFU, with prophylactic pegfilgrastim is associated with improved tolerability and equivalent RR compared to full dose FOLFIRINOX in advanced PC. The impact of dose attenuations on toxicity and efficacy warrants further evaluation in both LAPC and MPC.

Second-line gemcitabine plus nab-paclitaxel (G+A) for advanced pancreatic cancer (APC) after first-line FOLFIRINOX: Single institution retrospective review of efficacy and toxicity.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 344-344 ◽  
Author(s):  
Yue Zhang ◽  
Howard S. Hochster ◽  
Stacey Stein ◽  
Jill Lacy
Keyword(s):  
Retrospective Review ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Cancer Center ◽  
Second Line ◽  
Single Institution ◽  
First Line ◽  
Grade 3 ◽  
Ecog Ps ◽  
Dose Reductions

344 Background: Gemcitabine (G) plus paclitaxel protein-bound particles for injectable suspension (Abraxane, A) is an active first line regimen for APC based on improved efficacy compared to G (Van Hoff, DD et al. J Clin Oncol 31, 2013 [suppl;abstr 4005]). However, there is a paucity of data regarding efficacy of G+A in pts who received prior FOLFIRINOX. To assess efficacy and tolerability of 2nd line G+A, we reviewed our single institution experience with G+A in APC pts who received 1st line FOLFIRINOX. Methods: We conducted a retrospective review of dose, toxicity, efficacy of second line G+A in FOLFIRINOX-treated APC pts treated at Yale Cancer Center between 12/2011 and 08/2013. Pts were treated until progression, unacceptable toxicity, or pt preference. Doses were at treating physician’sdiscretion. Dose densities were compared to full doses (A 125 mg/m2 + G 1000 mg/m2 days 1, 8,15 q 4 wks). Response rate, med time to treatment failure (TTF), med overall survival (OS) were calculated. Results: 23 pts were treated with G+A after 1st line FOLFIRINOX. Pts characteristics: metastatic, 18; locally advanced, 5; med age, 61 (range 50-74);male, 9; ECOG PS ≤1, 22; med # FOLFIRINOX cycles, 12 (range 5-46). Med interval from FOLFIRINOX to G+A was 5 wks (range 1.7-40.3). Responses by RECIST were: PR, 2 (8.7%); SD for ≥7 wks, 8 (34.8%); PD, 10 (43.4%); ineval, 3 (13.1%). 9 (39%) and 8 (34%) pts had >30% decrease in CA 19-9 and CEA, respectively. 13 pts died, 6 pts stopped G+A, 4 pts are still receiving G+A. Med TTF was 11 wks (range 1-35). Med OS was >17.9 wks (range 2.1-69.6). All pts had initial dose reductions of G or A; 7 and 12 pts required further dose reductions with A and G, respectively. Dose densities were 56.9% and 63.5% for A and G, respectively. Grade ≥3 hematologic toxicities included neutropenia 17%, anemia 26%, thrombopenia 26%. Conclusions: In this single institution pt population, G+A has limited activity after FOLFIRINOX. Most of our pts received FOLFIRINOX for >6 months and were still able to receive a 2nd line doublet. Most required dose reductions for cytopenias, but this sequence was tolerable. In this setting, an additional 11 wks med TTF is about half of the TTF in 1st line G+A and may be clinically valuable.

Interim analysis of a phase II study of dose-modified FOLFIRINOX (mFOLFIRINOX) in locally advanced (LAPC) and metastatic pancreatic cancer (MPC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 256-256 ◽  
Author(s):  
Edward Samuel James ◽  
Xiaopan Yao ◽  
Xiangyu Cong ◽  
Stacey Stein ◽  
Kristin Kaley ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Interim Analysis ◽  
Historical Data ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Sensory Neuropathy ◽  
Open Label ◽  
Grade 3 ◽  
Ecog Ps

256 Background: Although FOLFIRINOX is superior to gemcitabine in MPC, the regimen is associated with significant toxicities (Conroy et al. N Engl J Med 2011;364:1817). In our prior retrospective analysis, efficacy was not compromised by dose attenuations of FOLFIRINOX (Gunturu et al. Med Oncol 2013;30:361). Based on this analysis, we are conducting a prospective phase II open label study to evaluate the efficacy & tolerability of mFOLFIRINOX in pts with advanced pancreatic cancer (PC). Methods: Previously untreated pts with MPC or LAPC received mFOLFIRINOX with 25% dose reductions of irinotecan & bolus 5-FU given every two wks until progression, unacceptable toxicity, or surgical resection. All pts received prophylactic pegfilgrastim. FDG-PET scans were obtained at baseline & after 2 cycles. CAT scans were obtained after every 4 cycles. Toxicities & response rate (RR) were compared to historical data reported by Conroy. Results: 53 pts with ECOG PS ≤1 have been enrolled to date between 11/11 and 08/13, Pt characteristics: LAPC 22; MPC 31; median age 62 yrs (range 46-86); male 30. Median # of cycles was 8 (range 1-21). Grade 3/4 toxicities were: anemia, febrile neutropenia (FN) & peripheral sensory neuropathy (PSN) – 3.8% each; ALT increased & thromboembolism – 5.7% each; diarrhea 7.5%; fatigue 11.3%; neutropenia 17%; thrombopenia 11.3% & vomiting 1.9%. Anemia ( p< 0.04), FN (p<0.04), PSN (p<0.04) and vomiting (p<0.02) were significantly decreased compared to historical data (Conroy). Response by RECIST (CR+PR) in 26 evaluable pts with MPC was 29% (0 CR, 9 PR, 14 SD, 3 PD) & similar to historical data (31.6%; p 0.85). 6/13 evaluable pts with LAPC underwent resection (46%).13/36 pts evaluable for PET response had a >50% decrease in SUV(max)(36%). Evaluation for OS & PFS is ongoing. Conclusions: Findings from our interim analysis suggests that mFOLFIRINOX, given along with prophylactic pegfilgrastim is associated with a similar RR and improved tolerability compared to full dose FOLFIRINOX in advanced PC. In pts with LAPC, neoadjuvant FOLFIRINOX appears to have substantial activity with 46% of evaluable pts undergoing resection. Accrual will continue to reach a goal of 70 pts. Clinical trial information: NCT01523457.

A phase Ib trial of FOLFIRINOX plus saridegib, an oral hedgehog (Hh) inhibitor, in pts with advanced pancreatic cancer (PDAC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3105-3105 ◽  
Author(s):  
Andrew H. Ko ◽  
Noelle K. LoConte ◽  
Emily Kantoff ◽  
Robert W. Ross ◽  
Elizabeth G. Trehu ◽  
...  
Keyword(s):  
Trial Design ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Clinical Trial Design ◽  
Concurrent Administration ◽  
Phase Ib ◽  
Grade 3 ◽  
Ecog Ps ◽  
Dose Levels

3105 Background: FOLFIRINOX has emerged as the optimal 1st-line treatment option for pts with advanced PDAC and good performance status; whether it can serve as the backbone upon which to add targeted agents in clinical trial design remains uncertain. The goal of this multicenter phase Ib study is to evaluate FOLFIRINOX in combination with saridegib, a novel oral agent that inhibits the Hh signaling pathway. In preclinical models of PDAC, saridegib increases chemotherapy delivery by depleting peritumoral stroma and increasing vascularity. Methods: Pts with previously untreated metastatic or locally advanced PDAC and ECOG PS 0-1 were eligible. Treatment consists of once-daily saridegib with concurrent administration of biweekly FOLFIRINOX (omitting the 5-FU bolus). A 3+3 dose escalation design was used (see dose levels below). Prophylactic WBC growth factor support is mandated.  DLT definitions include ALT/AST ≥10x ULN, grade 4 plts or ANC ≥5 d, or grade 3-4 nonheme toxicity. CT scans are obtained every 4 cycles. Limited PK analyses are performed. Results: Seven pts have been enrolled at the first 2 dose levels. Grade 1-2 AEs include GI (N/V/D), dehydration, fatigue, and LFT abnormalities. There was one DLT (grade 3 ALT elevation) at DL2. Other serious toxicities seen include grade 3 nausea (DL1) and grade 3 diarrhea (DL2). Tumor shrinkage has been observed in all 4 pts at DL1, ranging from 17-54%, with 2 unconfirmed PRs. Final MTD determination and updated safety and efficacy data will be presented at the meeting. Conclusions: A modified FOLFIRINOX regimen can be safely administered in combination with novel agents in clinical trials of PDAC. While saridegib was not beneficial when added to gemcitabine in a separate randomized phase II study, early evidence of significant responses on the current trial suggests that a more intensive chemotherapy platform may represent a preferable strategy in PDAC trial design. [Table: see text]

Gemcitabine (G) plus nab-paclitaxel (nab-P) plus chemoradiation (CRT) in locally advanced pancreatic cancer (LAPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14714-e14714
Author(s):  
Olugbenga Olanrele Olowokure ◽  
Ivan Dario Bedoya ◽  
Michelle Lynn Mierzwa ◽  
Maria Patricia Torregroza ◽  
Alok kumar Dwivedi ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Categorical Variables ◽  
Rank Test ◽  
Nccn Guidelines ◽  
Prior Therapy ◽  
Significant Difference ◽  
Ecog Ps ◽  
The Impact

e14714 Background: 30-40 % of PC pts present with LAPC. Optimal management remains controversial. Current NCCN guidelines, suggests clinical trial, FOLFIRINOX, G, G based combination therapy, chemo followed by CRT as options in pts with good PS. This single institution retrospective review, evaluated the UC experience of the impact of G+nab-p+/- CRT in LAPC. Methods: From 05/01/09-09/01/11,105 newly registered pts were identifiedusing ICD code 157, 13pts met inclusion criteria: ECOG PS 0-2, histologically proven LAPC, without prior therapy that received G + nab-P, pre or post radiation as part of their treatment. G+nab-p was given as cycles of G=1,000mg/m2 and nab-P=100mg/m2 weekly x3 every 4 weeks with appropriate modifications. CT scans and CA19-9 levels were followed. PFS was estimated from the date of diagnosis to date of progression or death if this occurred first and OS was estimated from date of diagnosis until date of death or loss to follow up. Kaplan Meier survival estimates were obtained with 95% confidence interval (CI). Log rank test was used to compare the PFS according to categorical variables. Results: Median duration of follow up was estimated to be 14.4 months (M) range(R) (5.8-19). CA19-9 data was available for 12 pts, 2 had baseline <1 (R<1-12,861), CA19-9 decrease > 50% from baseline was seen in 9/10. Mean # of G+nab-P cycles administered was 3, R (1-10). 77% received G based CRT with only 1pt receiving this post op. 38% (5/13) underwent resection, 4 post CRT with R0 margins and -ve LN’s and 1 pre CRT with R0 margins but 1/13 LN’s +ve. 11 pts were evaluable for response by RECIST (4PR, 6SD, 1PD). Disease control rate 91%. PFS 92% (CI: 57- 99%) at 6 M and 65% (CI: 31-85%) at 12 M. OS was 85% (CI: 51-96%) at 6M and 77 %(CI: 44-92%) at 12M. At 6M, 100% PFS was observed in resected group, whereas 88% PFS in non-resected group (p=0.12). There was no significant difference in PFS according to gender (p=0.44) and T lesion (p=0.49). Grade III/IV toxicity was mainly hematologic and gastrointestinal. (4/7) 57% received further therapy upon progression. Conclusions: Compared to contemporary G- based trials, the UC experience of G+ nab-P with CRT appears to be associated with improved survival in LAPC and warrants further study.

Phase I Trial Evaluating the Safety of Bevacizumab With Concurrent Radiotherapy and Capecitabine in Locally Advanced Pancreatic Cancer

2006 ◽  
Vol 24 (7) ◽  
pp. 1145-1151 ◽  
Author(s):  
Christopher H. Crane ◽  
Lee M. Ellis ◽  
James L. Abbruzzese ◽  
Christina Amos ◽  
Henry Q. Xiong ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Duodenal Mucosa ◽  
Duodenal Perforation ◽  
Bleeding Events ◽  
Duodenal Ulcers ◽  
Concurrent Radiotherapy ◽  
Perioperative Complication ◽  
Grade 3 ◽  
Dose Reductions

Purpose To study the safety of bevacizumab with capecitabine-based chemoradiotherapy. Patients and Methods Patients with inoperable pancreatic adenocarcinoma received bevacizumab 2 weeks before radiotherapy (50.4 Gy treating the primary tumor and gross adenopathy), every 2 weeks during radiotherapy (12 patients each at 2.5, 5.0, 7.5, and 10 mg/kg), and after radiotherapy until disease progression. Capecitabine was administered on days 14 through 52 (650 mg/m2 orally twice daily for the first six patients; 825 mg/m2 for the remaining patients). Results Significant acute gastrointestinal (43% grade 2; 4% grade 3), hand and foot syndrome (21% grade 2), and transient hematologic (8% grade 3 or greater) events were uncommon with protocol mandated dose reductions of capecitabine grade 2 toxicity (43% of patients). Among the first 30 patients treated, three patients had tumor-associated bleeding duodenal ulcers, and one had a contained duodenal perforation. No additional bleeding events occurred among the final 18 patients after patients with duodenal involvement by tumor were excluded. Nine (20%) of 46 assessable patients had confirmed partial responses until distant progression for a median of 6.2 months. Four patients have undergone pancreaticoduodenectomy without perioperative complication. The median survival was 11.6 months (95% CI, 9.6 to 13.6), from the start of protocol therapy. Conclusion Concurrent bevacizumab did not significantly increase the acute toxicity of a relatively well-tolerated chemoradiotherapy regimen. However, ulceration and bleeding in the radiation field possibly related to bevacizumab occurred when tumor involved the duodenal mucosa. The encouraging efficacy end points suggest that the further study of bevacizumab with chemoradiotherapy is warranted.

Phase I study of nivolumab (Nivo) + nab-paclitaxel (nab-P) + gemcitabine (Gem) in advanced pancreatic cancer (APC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 298-298 ◽  
Author(s):  
Zev A. Wainberg ◽  
Howard S. Hochster ◽  
Edward Jae-Hoon Kim ◽  
Ben George ◽  
Aparna Kalyan ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Liver Function Tests ◽  
Treatment Naïve ◽  
Grade 3 ◽  
Ecog Ps

298 Background: Chemotherapy may work synergistically with immune checkpoint inhibitors by increasing tumor antigen exposure. This 2-part phase I study assessed safety and efficacy of Nivo + nab-P + Gem in APC. Methods: Treatment-naive patients (pts) with APC (locally advanced or metastatic) received nab-P 125 mg/m2 + Gem 1000 mg/m2 on d 1, 8, and 15 + Nivo 3 mg/kg on d 1 and 15 of each 28-d cycle until disease progression (PD), unacceptable toxicity, or withdrawal. Pts could continue Nivo alone beyond initial PD. Part 1 assessed dose-limiting toxicities (DLTs) and determined the recommended Part 2 dose; Part 2 (expansion phase) further assessed safety. The primary endpoints were DLTs (Part 1) and safety and tolerability (Parts 1 and 2). Key secondary endpoints were response rates, progression-free survival (PFS), and overall survival (OS). Results: As of July 13, 2018, 50 pts with APC were treated: 6 in Part 1; 44 in Part 2. The median age was 67.5 years; 56% were male; 62% had an ECOG PS 1. Of 40 pts with available data, 12 (24%) had ≥ 1% and 6 (12%) had ≥ 5% PD-L1 expression at baseline (data missing for 10 pts). The median follow-up was 11.3 mo. In Part 1, 1 DLT (hepatitis, as evidenced by grade 3 elevated liver function tests; suspected to be related to nab-P + Gem) was reported. In Parts 1 and 2, 48 pts (96%) had ≥ 1 grade 3/4 TEAE; 7 (14%) discontinued treatment due to a TEAE. Most common (> 10%) grade 3/4 TEAEs of special interest were anemia (36%), neutropenia (36%), gastrointestinal events (24%), hepatic toxicity (22%), peripheral neuropathy (16%), thrombocytopenia (12%), and colitis (12%). One grade 5 TEAE, respiratory failure (most likely pneumonitis), was reported. The table shows treatment responses. Of 7 pts (14%) who continued Nivo beyond initial PD, 4 achieved disease control. The median PFS was 5.5 mo (6-mo PFS rate, 47%). The median OS was 9.9 mo (6-mo OS rate, 73%). Conclusions: Combining Nivo with nab-P + Gem is feasible in pts with APC: 1 DLT was reported, and no unexpected safety signals were detected. Clinical trial information: NCT02309177. [Table: see text]

FOLFIRINOX for advanced pancreatic cancer: The Princess Margaret experience.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 417-417 ◽  
Author(s):  
Muralidharan Chllamma ◽  
Natalie Cook ◽  
Kazim Giby ◽  
Anna Dodd ◽  
Lisa Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Pancreatic Head ◽  
Validated Questionnaire ◽  
Significant Difference ◽  
Starting Dose ◽  
Grade 3 ◽  
Dose Reductions

417 Background: The FOLFIRINOX regimen has been shown to significantly increase both overall (OS) and progression free (PFS) survival in metastatic pancreas cancer (MPC), albeit with an increase in adverse events (AEs). It is not known whether initial dose reductions compromise FOLFIRINOX efficacy and there are limited data regarding treatment of locally advanced pancreatic cancer (LAPC). Methods: We conducted a retrospective review of patients (pts) treated with FOLFIRINOX for MPC or LAPC at Princess Margaret Cancer Centre, and began treatment between Dec 2011 and April 2014. The primary objective was to evaluate the efficacy and safety of FOLFIRINOX when used with dose modifications. Results: 102 pts were identified; 66 MPC and 36 LAPC. Median age was 65 years. 72% of pts had pancreatic head tumors. At baseline 95% of pts had an ECOG performance status of 0 or 1; 95% had bilirubin < 1.5 ULN and 45% had a biliary stent. 68% of pts initiated treatment with a dose reduction (93% reduction or omission of bolus 5FU, 88% reduction in Irinotecan, 68% reduction in Oxaliplatin and 66% reduction in infusional 5FU). Median number of cycles was 6 (1-31); 25% of pts received <4 cycles. Median OS in metastatic pts was 12.9 months (mo) and 23 mo in LAPC; Median PFS was 8.7 mo (metastatic) and 11.1 mo in LAPC. There was no significant difference in PFS (10.9 vs. 10.3 mo; p=0.60) or OS (11.1 vs. 14.0 mo; p=0.19) between the full starting dose and reduced starting dose groups respectively. Partial response or stable disease was achieved in 57% of pts; 11% of the LAPC pts had a surgical resection. Grade 3/4 hematologic AEs were observed in 43% of pts (febrile neutropenia in 6%). Only 13% of pts received G-CSF support. Grade 3/4 non-hematologic AEs were observed in 28% of pts, including vomiting (19%), nausea (16%) and diarrhea (16%). 18% of pts had a treatment related hospitalization (5% neutropenic sepsis, 13% GI toxicity/dehydration.) There was one treatment related death. Pt wellbeing (scored on a validated questionnaire) significantly improved from baseline to cycle 4 (p=0.002). Conclusions: Modest dose reductions do not appear to compromise efficacy of FOLFIRINOX. Our median PFS, OS and AEs are comparable to other studies using FOLFIRINOX in both LAPC and metastatic disease.

The impact of dose modification or termination of S-1 as adjuvant therapy on survival of locally advanced gastric cancer underwent curative gastrectomy.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 193-193
Author(s):  
Takeshi Kawakami ◽  
Nozomu Machida ◽  
Etsuro Bando ◽  
Kaori Hayashi ◽  
Hiromichi Shirasu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factors ◽  
Adjuvant Therapy ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Cancer Center ◽  
Inclusion Criteria ◽  
Dose Modification ◽  
Ecog Ps ◽  
The Impact

193 Background: Adjuvant S-1 therapy for pStage II/III gastric cancer (GC) patients (pts) after curative resection is standard treatment in Japan, however, prognosis of pStage III is still poor. There are few reports investigating the association of treatment exposure with survival. Therefore, we investigated the impact of dose modification or termination of S-1 as adjuvant therapy on overall survival (OS). Methods: The data of locally advanced GC pts who underwent gastrectomy with D2 lymph-node dissection in Shizuoka Cancer Center between Jan 2007 and Aug 2013 were retrospectively collected. Inclusion criteria were as follows: age 20 to 80 years; ECOG PS 0 or 1; histologically proven adenocarcinoma; pStage III under TNM 7th edition; R0 resection; initiation of S-1 within 56 days after surgery. S-1 was administered for 4 weeks followed by a 2 weeks rest. We defined completion of planned S-1 therapy as continuation of S-1 one year after surgery. Results: One hundred and six pts satisfied inclusion criteria. Pts’ characteristics were as follows: median age, 67 years (range, 38-78); male/female, 77/29 pts; ECOG PS 0/1, 72/34 pts; primary tumor location EGJ/U/M/L, 1/27/45/33 pts; and pStage IIIA/IIIB/IIIC, 25/41/40 pts. Fifty-five pts (51%) needed dose modification (dose reduction and/or schedule alteration). Eighty-two pts (77%) achieved completion of planned S-1 therapy. Five year OS rate was 59.9%. Among potential prognostic factors for OS in univariate analysis (age, PS, pStage, completion of planned S-1 therapy, dose modification), completion of planned S-1 therapy (HR 0.26; 95% CI 0.13-0.51; p < 0.001) and PS 0 (HR 0.52; 95% CI 0.27-0.99; p = 0.048) were good prognostic factors and dose modification was not prognostic factor (HR 1.06; 95% CI 0.53-2.12; p = 0.876) for OS. Conclusions: This study suggested that completion of planned adjuvant S-1 therapy and PS 0 were good prognostic factors for OS and appropriate dose modification might not worsen their prognosis.

Phase I/II trial of dose reduced capecitabine in elderly or frail patients with untreated advanced colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 745-745
Author(s):  
Daniel Adam Breadner ◽  
Stephen Welch ◽  
Derek J. Jonker ◽  
Paul Klimo ◽  
M. Christine Cripps ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Advanced Colorectal Cancer ◽  
Frail Patients ◽  
Optimal Dosing ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
Dose Reductions

745 Background: Capecitabine (Cape) was initially assessed at a dose of 2500 mg/m2 in young or robust patients that do not represent the population in which oncologists consider Cape monotherapy in advanced colorectal cancer (aCRC). In practice Cape is frequently given to elderly or frail patients at 2000 mg/m2 but the optimal dosing remains controversial. Methods: A multi-centered phase I/II trial of reduced dose Cape 2000 mg/m2 d1–14 q21d was conducted in 221 patients in one or more of the following subsets: age65 years (167 pts), ECOG PS 1 (139 pts), elevated LDH (105 pts), prior pelvic RT (54 pts). Results: Median age was 72 years. A median 5 and mean 8 cycles were given (range 0 to 50). The phase I portion of the study determined prior pelvic radiation required dose reduction to 1500 mg/m2 for diarrhea. Grade 3/4 toxicity occurred in 25% of patients during the first 3 cycles (8.1% hand-foot syndrome, 7.7% diarrhea). Dose reductions were required in 14% and dose delays in 21%. Response rate is 13.6%, with 69.7% disease control rate. Median PFS was 5.6 months. Post progression 125 patients (67%) received further chemotherapy, 56 received further Cape monotherapy with a median of 4 additional cycles. Median overall survival for all patients is 14.3 months. Median survival was significantly higher for baseline ECOG 0 vs. ≥ 1 and normal vs. elevated LDH. When comparing patients receiving 2000 compared to 1500 mg/m2 the ORR was 19% vs. 17%, and the DCR was 73% vs. 63%. Median PFS was 5.9 vs. 4.7 months, and the OS was equal at 14.3 months. Hand-foot syndrome was more common at the higher dose, 46% vs. 30%, any grade. Conclusions: This report suggests dose reduced Cape has less toxicity compared to full dose, with only a small tradeoff in efficacy seen as a lower ORR. However, its improved tolerability likely leads to an increased number of cycles of therapy, and the PFS seems consistently higher at the lower dose. This trial reduces uncertainty regarding further dose reductions to 1500 mg/m2 for frail patients, in whom quality of life may be paramount. This should be viewed as compelling evidence, in the absence of a head to head clinical trial, that 2000, or even 1500, mg/m2 is an appropriate dose in elderly or frail patients with aCRC.

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