Retrospective comparison of modified FOLFIRINOX with full-dose FOLFIRINOX for advanced pancreatic cancer: A Japanese cancer center experience.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 469-469 ◽  
Author(s):  
Akihiro Ohba ◽  
Hideki Ueno ◽  
Yasunari Sakamoto ◽  
Shunsuke Kondo ◽  
Chigusa Morizane ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dose Reduction ◽  
Advanced Pancreatic Cancer ◽  
Group Versus ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Control Group ◽  
Phase 2 ◽  
Full Dose ◽  
Grade 3

469 Background: Various modified FOLFIRINOX (mFFX) regimens have been reported and widely used in clinical practice. Although there are retrospective studies and single-arm phase 2 studies comparing modified regimens to the full-dose regimen of the historical control group, head-to-head comparisons in the same population are limited. This study aimed to compare mFFX with full-dose FOLFIRINOX (fFFX) in patients with advanced pancreatic cancer (APC). Methods: We reviewed 85 patients with APC who received mFFX (no bolus fluorouracil and irinotecan 150 mg per square) or fFFX as first-line chemotherapy between January 2014 and December 2016. mFFX has been used since January 2016 on the basis of results of a Japanese phase 2 study. The efficacy, safety, and dose reduction pattern were evaluated. Results: A total of 56 eligible patients (26 treated with mFFX and 30 with fFFX) were selected. Baseline characteristics of each group were well-balanced. The median relative dose intensities of oxaliplatin, irinotecan, bolus fluorouracil, and continuous infusion fluorouracil were 68.6%, 78.5%, 0%, and 88.5% in the mFFX group, and 80.5%, 76.5%, 25.6%, and 83.6% in the fFFX group, respectively. Second cycle dose reduction occurred in 38% of the patients in the mFFX group and in 62% of those in the fFFX group. The median overall survival (OS) was 19.0 months in the mFFX group, compared to 13.2 months in the fFFX group (HR 0.60, 95% CI 0.25–1.47, P = 0.27). In a multivariate analysis to adjust for prognostic factors for OS, the hazard ratio for death with mFFX was significant (adjusted HR 0.36, 95% CI 0.14–0.93, P = 0.04). The median progression-free survival was 8.3 months in the mFFX group and 5.9 months in the fFFX group (HR 0.83, 95% CI 0.44–1.54, P = 0.55). The response rate was 35% in the mFFX group versus 30% (P = 0.78) in the fFFX group, respectively. Grade 3 or 4 leucopenia (15% versus 40%), neutropenia (42% versus 70%), febrile neutropenia (8% versus 17%), and nausea (4% versus 13%) were decreased in the mFFX group, but the differences were not statistically significant. Conclusions: mFFX had equivalent or higher efficacy and improved safety compared to fFFX in the same population.

Helical tomotherapy and concurrent gemcitabine-based chemotherapy for locally advanced pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 318-318
Author(s):  
Jinsil Seong ◽  
Jisuk Chang ◽  
Siyoung Song ◽  
Woong Keum
Keyword(s):  
Pancreatic Cancer ◽  
Helical Tomotherapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
Full Dose ◽  
Gi Toxicity ◽  
Grade 3

318 Background: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between May 2006 and May 2009. Radiotherapy was directed to the primary tumor with a 0.5 cm margin without prophylactic nodal coverage. Twenty nine patients (79%) received full-dose (1000 mg/m2) gemcitabine based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range 3.4-43.9) for the entire cohort, and 22.5 months (range 12.0-43.9) for surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (20%) were converted to resectable status, including one with a pathologic complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than grade 3. Severe late GI toxicity (≥ Grade 3) occurred in 10 patients (26%); one treatment related death due to GI bleeding was observed. Conclusions: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Kotone Hayuka ◽  
Hiroyuki Okuyama ◽  
Akitsu Murakami ◽  
Yoshihiro Okita ◽  
Takamasa Nishiuchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

<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.

scholarly journals Real-world comparative effectiveness of nab-paclitaxel plus gemcitabine versus FOLFIRINOX in advanced pancreatic cancer: a systematic review

2019 ◽  
Vol 11 ◽  
pp. 175883591985036 ◽  
Author(s):  
Elena Gabriela Chiorean ◽  
Winson Y. Cheung ◽  
Guido Giordano ◽  
George Kim ◽  
Salah-Eddin Al-Batran
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Real World ◽  
Controlled Trial ◽  
Safety Data ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Eligibility Criteria ◽  
Grade 3

Background: No clinical trial has directly compared nab-paclitaxel/gemcitabine (nab-P/G) with FOLFIRINOX (fluorouracil/leucovorin/oxaliplatin/irinotecan) in metastatic or advanced pancreatic cancer (mPC or aPC). We conducted a systematic review of real-world studies comparing these regimens in the first-line setting. Methods: Embase and MEDLINE databases through 22 January 2019, and Gastrointestinal Cancers Symposium 2019 abstracts were searched for real-world, retrospective studies comparing first-line nab-P/G versus FOLFIRINOX in mPC or aPC that met specific parameters. Studies with radiotherapy were excluded. Study quality was assessed using the Newcastle–Ottawa Scale. Results: Of 818 records initially identified, 35 were duplicates and 749 did not meet the eligibility criteria, mostly because they were either not comparative ( n = 356) or not first line ( n = 245). The remaining 34 studies (21 mPC; 13 aPC) assessed >6915 patients who received nab-P/G or FOLFIRINOX. In the studies identified, the median overall survival (OS) reached 14.4 and 15.9 months with nab-P/G and FOLFIRINOX, respectively, and median progression-free survival reached 8.5 and 11.7 months, respectively. Safety data were reported in 14 studies (2205 patients), including 8 single-institutional studies. In most single-institutional studies that reported safety data, rates were higher with FOLFIRINOX versus nab-P/G for grade 3/4 neutropenia (five of six studies) and febrile neutropenia (all three studies), while rates of grade 3/4 peripheral neuropathy were higher with nab-P/G in four of seven studies. Conclusions: Although FOLFIRINOX was associated with slightly longer median OS in more studies, the differences, when available, were not statistically significant. Therefore, a randomized, controlled trial is warranted. Toxicity profile differences represent key considerations for treatment decisions.

Efficacy and safety of 5-fluorouracil (5-FU) / levofolinate / irinotecan (FOLFIRI) for previously treated advanced pancreatic cancer (APC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 407-407
Author(s):  
Hiromichi Shirasu ◽  
Takeshi Kawakami ◽  
Satoshi Hamauchi ◽  
Takahiro Tsushima ◽  
Akiko Todaka ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Treatment Cycle ◽  
Initial Dosage ◽  
Advanced Pancreatic Cancer ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Line Treatment ◽  
Median Treatment ◽  
Treatment Line

407 Background: 5-fluorouracil (5-FU) / levofolinate / irinotecan (FOLFIRI) is one of the preferred regimens for patients (pts) with advanced pancreatic cancer (APC) who received prior gemcitabine-based therapy in the National Comprehensive Cancer Network Guidelines. However, its survival benefit or safety in clinical practice is unclear. Methods: We retrospectively assessed the data of consecutive pts with APC who received FOLFIRI as a second or later-line treatment after gemcitabine-based therapy at Shizuoka Cancer Center between May 2014 and March 2020. Results: The characteristics of 102 pts included in this analysis were as follows: median age (range), 67 (39-78) y; male/female, 55/47; ECOG PS0/1/2, 21/72/9; the number of metastatic sites 0/1/2/3/4, 7/48/35/8/4; unresectable/recurrent, 84/18; UGT1A1 status wild/*6 or*28 heterozygous/homo or double-heterozygous/unknown, 40/40/5/17; treatment line of FOLFIRI 2nd/3rd/4th, 64/32/6. Previous treatment history according to the treatment line of FOLFIRI was as follows: 2nd-line, all patients received GEM-based regimen, GEM plus nanoparticle albumin bound paclitaxel in 63 pts (98.4%) and GEM in 1 (1.6%); 3rd, GEM-based and S1 in 20 (62.5%), GEM-based and 5-FU/levofolinate/oxaliplatin (FOLFOX) in 12 (37.5%); 4th, GEM-based, FOLFOX and S-1 or other agent in 5 (83.3%), 2 GEM-based regimens and S1 in 1 (16.7%). The median treatment cycle was 5 (range 1-55). The median treatment cycle according to the treatment line was as follows: 2nd-line, 7(1-55); 3rd, 4(1-14); 4th, 3.5(1-10). The initial dosage for each cytotoxic agent was as follows: bolus 5-FU injected/omited 72/30; continuous 5-FU 2400/2000/1200 mg/m2, 88/13/1; irinotecan 180/150/120/less than or equal to 100mg/m2, 27/59/13/3. The overall response rate (ORR) and disease control rate (DCR) were 5.9% and 52.9%, respectively. ORR and DCR according to the treatment line were as follows: 2nd-line, 9.3/64.1%; 3rd, 0/68.8%; 4th, 0/50.0%. At the median follow up 6.5 M, the median overall survival (OS) and progression free survival (PFS) were 6.6M and 3.1M, respectively. The median OS and PFS according to the treatment line were as follows: 2nd-line, 8.1/3.6M; 3rd, 5.1/2.1M; 4th, 6.6/2.0M. Adverse events (AEs) were observed in 70.8% pts. Grade 3 or higher AEs occurred in 27.2% pts [neutropenia in 26 (25.2%) pts, febrile neutropenia in 4 (3.9%) pts, nausea in 4 (3.9%) pts, decreased appetite in 3 (2.9%) pts]. No treatment related deaths were observed. Conclusions: FOLFIRI is well tolerated and effective especially in the second-line treatment for pts with gemcitabine-refractory APC.

Phase II study of alternate-day oral therapy with S-1 for unresectable advanced pancreatic cancer: An updated report.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 252-252
Author(s):  
Sohei Satoi ◽  
Motoki Miyazawa ◽  
Masaji Tani ◽  
Manabu Kawai ◽  
Seiko Hirono ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Effects ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Current Data ◽  
Standard Regimen ◽  
Grade 3

252 Background: Based on the results of GEST, S-1 was confirmed to be non-inferior to gemcitabine. However, the recommended regimen of 4 weeks of administration interrupted by 2 weeks of drug withdrawal frequently causes adverse effect. Grade3/4 toxicities (%) in S-1 were neutropenia 8.8, anorexia 11.4, diarrhea 5.5. On the other hand, we experienced in clinical practice that the alternate-day administration of S-1 reduced adverse effects and was tolerable for unresectable advanced pancreatic cancer patients unwilling to continue the standard daily administration. We therefore conducted a multi-center cooperative prospective study to compare daily with alternate-day administration of S-1 for unresectable advanced pancreatic cancer. Methods: Patients with unresectable advanced pancreatic cancer (PS, 0 to 1; age, 20 to 80 years; no other therapy) were eligible for enrollment in this trial. S-1 was administered a dose of 40 to 60 mg twice daily, assigned according to body-surface area, on Monday, Wednesday, Friday, and Sunday (specified days). Each treatment cycle will be 42 days (6 weeks). The primary endpoint was overall survival (OS). Secondary endpoints were safety, response rate (RR), progression free survival (PFS), time to treatment failure (TTF). Results: A total of 50 patients were enrolled from Sep 2009 to Feb 2011. 48 patients were evaluable for response. Male/Female was 21/27, PS: 0/1 was 40/8. With a median follow-up time of 28.2 months, OS as primary endpoint was 8.4 months (95% CI, 5.4-10.8) with the 1 year survival rate 29.2%. PFS was 5.5 months, and TTF was 3.9 months. RR was 10.4% (95% CI: 3.5-19.1), and Disease Control rate was 79.2%. Grade 3/4 hematological and non-hematological toxicities were minor. All of those adverse reactions were tolerable and reversible. Conclusions: We will report the data from the final analysis at this meeting. The current data show mitigation of adverse effects with alternate-day administration of S-1, and it appears to be a more sustainable option for unresectable advanced pancreatic cancer. A randomized phase II trial comparing this regimen of S-1 with standard regimen of S-1 is ongoing. Clinical trial information: 000003453.

Gemcitabine (Gem) and nab-paclitaxel (nab-P) in patients (pts) with refractory advanced pancreatic cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 413-413 ◽  
Author(s):  
Sofia Palacio ◽  
Ikechukwu Immanuel Akunyili ◽  
Vinicius Ernani ◽  
Jessica Macintyre ◽  
Jaime R. Merchan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Benefit ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Second Line ◽  
Positive Interaction ◽  
Line Therapy ◽  
Third Line

413 Background: The combination of nab-P and Gem improves survival compared to Gem alone in first-line therapy of metastatic pancreatic cancer. Efficacy data with this doublet in previously treated pts are scant. Our group presented preliminary results on 10 pts treated with this two-drug combination in the second and third line setting and herein present updated data on 59 pts. Methods: This IRB approved analysis identified all pts diagnosed with advanced refractory pancreatic cancer, treated with second-line Gem and nab-P at University of Miami and Sylvester Comprehensive Cancer Center between September 2010 and June 2014. Response by RECIST, CA19-9, and symptomatic improvement were assessed. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of Gem + nab-P and were analyzed using the Kaplan-Meier method. Clinical benefit was defined as the percentage of patients with a partial response (PR) or stable disease (SD). Results: Data from59 pts were analyzed. The median age was 60; 55% were male; 54% received Gem + nab-P as second line therapy and 46% received it as third-line or beyond. Five (10%) pts had confirmed PR, 23 (47%) SD and 21 (43%) progressed. Among the 31 (52%) pts who received prior Gem, 18 (58%) had clinical benefit, 3 PR and 15 SD. The median OS was 3.9 months. The median PFS was 3 months. Toxicity appears similar to what has been reported on the MPACT trial with the combination. Conclusions: The clinical benefit seen withGem and nab-P in this group of pretreated pancreatic cancer pts suggests that it can be considered as an option. Additionally, prior Gem treatment appears not to decrease Gem and nab-P benefit in this population. Since nab-P monotherapy has modest activity in pre-treated pancreatic cancer pts, our data suggests a positive interaction between Gem and nab-P that may overcome resistance to Gem. [Table: see text]

Second-line pemetrexed–oxaliplatin combination for advanced pancreatic adenocarcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15597-e15597
Author(s):  
M. Mazzer ◽  
E. Zanon ◽  
L. Foltran ◽  
F. De Pauli ◽  
G. Cardellino ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Second Line ◽  
Free Survival ◽  
Full Sample ◽  
Ca 19.9 ◽  
Grade 3 ◽  
Α Level ◽  
Vitamin B12 Supplementation

e15597 Background: Few regimens showed efficacy in advanced pancreatic cancer patients (pts) who had failed a first-line gemcitabine-based therapy. However, there is growing evidence suggesting that second-line treatment may provide further disease control in selected pts. Both pemetrexed and oxaliplatin demonstrated activity in this setting, and their combination resulted safe and tolerable.Methods: Pancreatic cancer pts with advanced disease, PS>60, age>18 years, who progressed after a gemcitabine-based therapy were enrolled in a phase II trial, and treated with pemetrexed 500 mg/mq followed by oxaliplatin 120 mg/mq, day 1 every 3 weeks, together with adequate oral folinic acid and intramuscular vitamin B12 supplementation. Accordingly to the Simon Minimax two-stage study design, an accrual of 31 patients was planned, with a minimum response rate considered of interest of 25%, α level 0.10 and β level 0.10. Results: To date, 16 patients have been treated. Of them, 12 progressed during or shortly after gemcitabine (13) or gemcitabine-cisplatin combination (3), with a median time to progression of 186 days. 62 cycles were delivered, with a median of 4 cycles per patient (range 2–8). Overall, the regimen was well tolerated: most common adverse events were mild-to-moderate sensory neurotoxicity and gastrointestinal disturbances. We reported grade 3 anemia, grade 3 thrombocytopenia, and grade 3 fatigue in 1 patient each. Three among the treated patients died within 30 days from last delivered cycle due to progressive disease. Confirmed partial (3) or minor responses (6) were observed in 9 out of 15 evaluable pts, with a median decrease in the Ca 19.9 value of 43% among those who responded. Median progression-free survival was 99 days. At the time of analysis, 3 out of 16 patients are still on treatment.Conclusions: The preliminary results suggest that second-line pemetrexed-oxaliplatin combination is well tolerated and reasonably active, and allow the continuation of the study until the full sample of 31 pts. No significant financial relationships to disclose.

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.

A retrospective analysis of data from two trials of sunitinib in patients with advanced renal cell carcinoma (RCC): Pitfalls of efficacy subgroup analyses based on dose-reduction status.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 363-363 ◽  
Author(s):  
Reza Khosravan ◽  
Xin Huang ◽  
Robin Wiltshire ◽  
Mariajose Lechuga ◽  
Robert John Motzer
Keyword(s):  
Dose Reduction ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Cancer Center ◽  
Phase 2 ◽  
Phase 3 ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Trough Concentrations ◽  
Require Dose

363 Background: Patients requiring sunitinib dose reduction who received a novel dose/schedule modification scheme had longer progression-free survival (PFS) than patients who did not require dose reduction and remained on 50 mg Schedule 4/2 (4 weeks on, 2 weeks off) (Bjarnason 2011). Our analysis compared sunitinib efficacy in advanced RCC patients with/without dose reduction using the label-approved, dose-reduction scheme (ie, 50 mg/37.5 mg/25 mg) and schedule (Schedule 4/2) and explored potential causes of any differences. Methods: Data from a Phase 3 and a Phase 2 trial, sunitinib Schedule 4/2 arms only (N=375 and 146, respectively), were retrospectively analyzed, and pharmacokinetics and baseline characteristics of patients with/without dose reduction compared. Results: In the Phase 3 trial, median (95% CI) PFS was 14.0 (13.1–16.2) months (mos) and 8.1 (6.3–10.6) mos with (n=194) and without (n=181) dose reduction, respectively. In the Phase 2 trial, corresponding PFS values were 13.4 (9.8–19.8) mos and 5.8 (3.9–8.5) mos (n=51 and 95, respectively). In the Phase 2 trial, steady-state mean (SD) total drug trough concentrations were 96.0 (42.2) ng/mL and 85.8 (43.4) ng/mL on Day 29 of Cycle 1 in patients with/without dose reduction, respectively. In both studies, the percent of patients with baseline Memorial Sloan-Kettering Cancer Center risk factors of 0 (favorable), 1–2 (intermediate), and 3 (poor) were 37–47%, 53–57% and 0–6% with dose reduction vs. 25–28%, 65–72%, and 0–10% without dose reduction. The mean (range) time to dose reduction was 7.2 (0.03–40.4) mos in the Phase 3 trial and 4.5 (0.4–22.6) mos in the Phase 2 trial. Conclusions: Patients with dose reduction remaining on Schedule 4/2 appeared to have longer PFS than patients with no dose reduction. The differences were not caused by differences in plasma drug exposures; they appeared to be due, at least in part, to 1) differences in patients’ baseline prognostic factors and 2) patients’ PFS or longevity affecting their dose-reduction status. Thus, efficacy subgroup analysis based on patients’ dose-reduction status appears to be confounded, leading to biased results.

Gemcitabine (G) and nab-paclitaxel (nab-P) in patients with refractory advanced pancreatic cancer (PC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 373-373
Author(s):  
Vinicius Ernani ◽  
Ikechukwu Immanuel Akunyili ◽  
Peter Joel Hosein ◽  
Jessica Macintyre ◽  
Caio Max S. Rocha Lima
Keyword(s):  
Chemotherapy Regimen ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Symptomatic Improvement ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Hematologic Toxicity ◽  
Standard Chemotherapy Regimen ◽  
Grade 3

373 Background: There is no standard chemotherapy regimen for PC patients who have progressed on G and fluoropyrimidine-based therapy. Single agent nab-P had limited activity on a second-line phase II trial in PC. Synergistic preclinical studies with G and taxanes have been reported. Nab-P targets stromal cells and leads to improved delivery of chemotherapy to PC cells. The combination of G + nab-P might be an effective approach in pretreated PC. Methods: A retrospective analysis of advanced refractory PC patients treated from Sep 2010 to Aug 2011 with the combination of G + nab-P was performed at the Sylvester Comprehensive Cancer Center. Patients received G 1000mg/m2 and nab-P 100mg/m2 on D1, 8 and 15 of a 28 day cycle. Treatment response was assessed by review of imaging studies using the RECIST criteria, CA19-9 response and symptomatic improvement. The progression-free survival (PFS) and overall survival (OS) were calculated from time of commencement of G + nab-P until documented progression or death respectively. Results: 10 patients were treated with G + nab-P; 60%, 30% and 10% of patients had received 3, 2 and 1 prior chemotherapy regimen. 90% and 80% received prior G or fluoropyrimidine-based regimen respectively. Therapy was discontinued in one patient following only one dose of G + nab-P (Cycle 1, day 1) due to grade 2 thrombocytopenia. The remaining 9 patients received a median of 4 cycles. Two (22.2%) patients had confirmed PR, 3(33.3%) patients had confirmed stable disease while 4 (44.4%) patients progressed on therapy. The median PFS was 13.7 weeks. The median PFS was 20 weeks in patients with PR or SD and 9.9 weeks in patients with PD. Recurrent malignant ascitis resolved in a patient with peritoneal carcinomatosis. Treatment was well tolerated; grade 3-4 hematologic toxicity included anemia, thrombocytopenia and neutropenia in 2, 1 and 2 patients respectively. 70% of patients required G-CSF support. Non hematologic Grade 3-4 toxicities included fatigue, peripheral neuropathy; nausea and vomiting in 3, 2 and 1 patient respectively. Conclusions: G + nab-P resulted in clinical benefit in half of this group of advanced PC patients who had previously progressed on G and fluoropyrimidine-based regimens.

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