Search

395 Background: Toxicities associated with FOLFIRINOX have prompted use of modifications, despite absence of prospective data validating comparable efficacy and improved tolerability. To determine the impact of attenuated doses of irinotecan and bolus 5FU on efficacy and tolerability, we conducted a prospective phase II study of modified FOLFIRINOX in advanced PC. The efficacy of a FOLFIRINOX regimen has not been previously examined in locally advanced PC (LAPC). Previous studies in LAPC have compared chemo vs chemoRT with median OS in the 9-12 mo range (Loehrer et al, Chauffert et al, Hammel et al). Methods: Previously untreated pts with MPC or LAPC received modified FOLFIRINOX with pegylated filgrastim. Irinotecan and bolus FU were reduced by 25%. AEs were compared to historical control (Conroy et al NEJM 2011). Objective RR in MPC was compared to historical control. PFS and OS were calculated for both cohorts. Results: 31 and 44 pts with LAPC and MPC enrolled. Treatment-related grade 3 and 4 AEs were diarrhea (16.2%), neutropenia (12.2%), fatigue (12.2%), thrombocytopenia (9.5%), anemia (5.4%). Neutropenia (p < 0.0001), vomiting (p = 0.001), and fatigue (p = 0.01) were significantly decreased compared to historical control patients. In MPC, the RR (35.1%) was similar to the historical control group (36.3%; p 0.82); median PFS and OS were 6.1 months (95% CI, 5.19 to 8.31) and10.2 months (95% CI, 7.65 to 14.32) respectively. In LAPC, the RR was 17.2% and median PFS and OS were 17.8 mo (95% CI, 11.0 to 23.9) and 26.6 mo (95% CI, 16.7, NA) respectively. 13 pts went on to surgical resection with 10 now alive and 6 without recurrence. We found no significant association between early metabolic response by FDG-PET imaging and PFS and OS. Conclusions: In this first prospective study of modified FOLFIRINOX, the regimen was well tolerated and associated with decreased incidence of AEs compared to historical control of standard FOLFIRINOX. In MPC pts, the efficacy of the modified regimen appear uncompromised. In this first prospective study of a FOLFIRINOX regimen in LAPC, the PFS and OS surpasses that of previously studied regimens in LAPC. Clinical trial information: NCT01523457.

769 Background: FOLFIRINOX (FFX) and Gemcitabine plus nab-paclitaxel (GN) are established first line (1L) therapies for metastatic pancreatic cancer (MPC) but real-world data on their comparative effectiveness is limited. Methods: All cases of MPC treated with 1L FFX or GN at Yale Smilow Cancer Hospital and the affiliated community care centers (CCC) from January 2011 – April 2019 were reviewed. Patient (pt) demographics, prior therapy, initial and subsequent dose reductions (DR), time to treatment discontinuation (TTD), overall survival (OS), and second line (2L) treatment data were manually abstracted from the electronic medical record. Categorical and continuous variables were compared between 1L FFX and GN cohorts via the Chi-squared and Wilcoxon rank-sum tests. Median OS was calculated by the Kaplan-Meier method. Results: We identified 363 MPC pts treated with 1L FFX or GN; 269 (74%) pts were treated with FFX and 94 (26%) with GN as 1L therapy. 204 (56%) pts were treated at the main campus and 159 (44%) at a CCC. Demographics and baseline characteristics (FFX/GN) were as follows: gender (male) 55% / 41%; race (white) 82% / 77%; age < 76 90% / 71% ( P < 0.001). 332 (91%) of pts received no prior therapy; 21 (6%) had prior surgery plus adjuvant gemcitabine and 10 (3%) had surgery alone. 98% of FFX-treated pts were treated with upfront DR, compared to 78% of GN-treated pts ( P= 0.003). 78% and 53% of FFX-treated and GN-treated pts, respectively, had subsequent DR ( P< 0.001). Median TTD was 4.8 months with FFX and 3.4 months with GN ( P= 0.0029) and the median OS was 11.3 months with FFX versus 7.2 months with GN ( P < 0.0001). After 1L, 33% and 61% of FFX- and GN-treated pts, respectively, received no further chemotherapy ( P< 0.001). Conclusions: In the largest manually abstracted retrospective analysis to date, MPC pts treated with 1L FFX were younger, more likely to receive 2L therapy, and had increased survival compared to pts treated with GN. The OS of pts treated with FFX was similar to the OS reported by Conroy et al despite upfront dose attenuations in 98% of pts. A randomized trial is needed to confirm optimal sequencing of chemotherapy in MPC.

Patients who receive neoadjuvant chemotherapy for locally advanced breast cancer and have four or more ipsilateral axillary lymph nodes involved at surgery are at high risk for recurrence, with a median time to relapse of 18 months. We offered such patients high-dose chemotherapy with stem cell rescue. Patients received cyclophosphamide or paclitaxel and granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells. Melphalan 140 mg/m2 was then given with stem cell rescue. Twenty-four to 35 days later, thiotepa 900 mg/m2 was given with stem cell rescue. Patients with hormone receptor-positive tumors received tamoxifen. We treated 14 patients in this fashion from 1995 to 1998. The mean age was 46.7 years. The majority of cancers were stage IIIB (79%). Thirteen women underwent mastectomy after anthracycline-containing chemotherapy and 50% had more than seven positive lymph nodes. Hospitalization was principally for neutropenic fever. Other morbidities were pneumonitis, cardiomyopathy, and grade 3/4 white blood cell (WBC) toxicity. No patient died of a treatment-related complication. Seven of 14 relapsed at 10, 12