A phase I/II study of S-1 plus oxaliplatin combined with radiation (SOX/RT) for preoperative locally advanced rectal carcinoma (JACCRO CC-04: SHOGUN trial).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 602-602
Author(s):  
Toshiaki Watanabe ◽  
Satoshi Matsusaka ◽  
Soichiro Ishihara ◽  
Keisaku Kondo ◽  
Hisanaga Horie ◽  
...  
Keyword(s):  
Phase I ◽  
Rectal Carcinoma ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Sphincter Preservation ◽  
Level 3

602 Background: Previous western trials of preoperative chemoradiation (CRT) in patients with locally advanced rectal carcinoma (LARC) have been shown to increase the chance of sphincter preservation and local control, and has become the standard of care in western countries. In Japan, preoperative CRT has not been utilized in LARC and its value is unconfirmed. Thus, we conducted a phase I/II study of preoperative CRT with S-1, which is widely used oral fluoropyrimidine in Japan to treat gastrointestinal cancer, plus oxaliplatin in patients with LARC. Methods: Patients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. A total radiation dose of 50.4 Gy was delivered in 28 fractions over 5 weeks, and S-1 was orally administered 40mg/m2 twice a day for 5 days a week at 1st, 2nd, 4th and 5th week. Oxaliplatin was administered at a dose of 40 mg/m2 (level 1), 50 mg/m2 (level 2) or 60 mg/m2(level 3) on day 1, 8, 22 and 29. Surgery was performed within 6-10 weeks after CRT. The primary endpoint of phase I part was to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of oxaliplatin. Primary endpoint of phase II was evaluated pathologic complete response (pCR) rate at RD. Results: 13 patients were enrolled in the phase I part, 2 dose-limiting toxicities (DLTs, skipping oxaliplatin due to the grade 2 neutropenia) occurred in the dose level 3, and the MTD was not reached. In phase II, 45 patients were treated at the RD of oxaliplatin (60 mg/m2) and 44 patients (97.8%) underwent surgery. A pCR was observed in 12 patients (27.3%). The relative dose intensity of radiation, S-1, oxaliplatin was 98.4%, 94.0%, and 94.3%, respectively. The incidence of grade 3-4 diarrhea and neutropenia was 8.9% and 2.2%, respectively. Postoperative complications of any grade occurred in 27.3% of patients. Conclusions: Preoperative CRT with S-1 plus oxaliplatin showed promising results in pathological responses and favorable toxicities profiles. Clinical trial information: NCT01227239.

Phase I study of cisplatin/carboplatin/irinotecan (CPI) regimen in patients with ED small-cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18202-18202
Author(s):  
M. Ichiki ◽  
Y. Yoshida ◽  
A. Ishimatsu ◽  
S. Minami ◽  
K. Taguchi ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Phase I Study ◽  
Phase Ii Study ◽  
Active Form ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Hematological Toxicity ◽  
Standard Regimen ◽  
Level 1

18202 Cisplatin/irinotecan(IP) is standard regimen for ED-SCLC in Japan. Cisplatin (CDDP)-based treatment requires copious hydration, which can lead to a deterioration of outpatients’ quality of life. CDDP and carboplatin (CBDCA) have a common active form, but are associated with different adverse reactions. We considered that the combined use of these two agents could increase the dose intensity of active form platinum complexes without enhancing their toxicities. The IP was modified to nearly half the dose of CDDP/CBDCA to facilitate outpatient administration. We conducted a phase I study to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of this modified regimen for patients with ED-SCLC and stage IV NSCLC. Eligibility criteria included: PS 0–1, age <75 yrs, no prior therapy, measurable disease, adequate organ functions. DLT was defined as follows: 1) grade 4 neutropenia lasting 4 days or febrile neutropenia, 2) grade 4 thrombocytopenia, 3) prolongation of treatment due to toxicity, 4) grade 3 or worse non-hematological toxicity. Three patients were enrolled at level 1(CDDP/CBDCA: 25 mg/m2/AUC2), 3 patients at level 2 (25 mg/m2/AUC 2.5) and 3 patients at level 3 (30 mg/m2/ AUC 2.5), respectively. DLT was not observed at level 1, 2, 3. At dose level 4 (30 mg/m2/AUC3), two of three patients experienced DLT, suggesting this level to be the MTD. The recommended dose for phase II study is CDDP 30 mg/m2 on day 1, CBDCA AUC 2.5 on day 1 and irinotecan 60 mg/m2 on days 1, 8, 15. A phase II study of this regimen in ED-SCLC is ongoing. No significant financial relationships to disclose.

Preoperative chemoradiation with S-1 plus oxaliplatin in patients with locally advanced rectal cancer: Results of a phase II study and the role of apparent diffusion coefficient (ADC) by diffusion-weighted magnetic resonance imaging (DW MRI) for prediction of pathologic responses.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 629-629
Author(s):  
E. M. Lee ◽  
J. L. Hong ◽  
J. L. Lee ◽  
S. Y. Kim ◽  
Y. S. Park ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Preoperative Chemoradiation ◽  
Curative Surgery

629 Background: We conducted a phase II study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients (pts) with locally advanced rectal cancer. Tumor ADCs were measured by DW-MRI and were evaluated as a predictive marker for pathologic responses. Methods: Radiotherapy was delivered to a total 50.4 Gy. The recommended doses were determined by a previous phase I study; oxaliplatin 50 mg/m2/week on D1, 8, 22 and 29, and S-1 80 mg/m2/day on D1-14 and D22-35. Total mesorectal excision was performed within 6 ± 2 weeks. Primary endpoint was pathologic complete response (pCR) rate. The value of tumor ADCs by DW-MRI was measured before and after CRT, and was correlated with pathologic responses after surgery. Results: A total of 38 patients were enrolled; 22 (57.9%) were men and the median age was 54 years (range, 28-67). Of 35 patients who underwent curative surgery, 28 patients underwent sphincter-saving operations. There was no grade 4 toxicity, and grade 3 toxicities included leukopenia (2.7%), neutropenia (2.7%), anorexia (2.7%), nausea (2.7%) and diarrhea (8.8%). The pCR rate was 25.7% (8/35, 95% CI [10.9-42.1]) and additional 10 patients (28.6%) showed near total regressions of tumor. Tumor ADCs by DW-MRI were calculated in 38 patients (including phase I part). The post-CRT ADC and the ADC changes (ΔADC) were significantly correlated with pCR rate (post-CRT ADC: 1.52±0.46 vs. 1.07±0.58, p=0.037, ΔADC: 44.5% vs. -7.6%, p=0.026). Conclusions: Preoperative CRT with S-1 plus oxaliplatin showed promising results in pathologic responses and favorable toxicities profiles. Tumor ADC by DW-MRI seems to be a useful method for predicting responses. No significant financial relationships to disclose.

Voltage: Investigator-initiated clinical trial of nivolumab monotherapy and subsequent radical surgery following preoperative chemoradiotherapy in patients with microsatellite stable locally advanced rectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3606-3606 ◽  
Author(s):  
Takayuki Yoshino ◽  
Hideaki Bando ◽  
Yuichiro Tsukada ◽  
Koji Inamori ◽  
Satoshi Yuki ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rectal Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Fisher Exact Test

3606 Background: Chemoradiotherapy (CRT) with surgery (S) is standard for patients (pts) with locally-advanced rectal cancer (LARC), and nivolumab (nivo) is active in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). We studied nivo and radical S following CRT (50.4 Gy with capecitabine 1,650 mg/m2) in T3–4 NanyM0 LARC. Methods: Phase I included testing of a recommended phase II dosing schedule (RP2S). Efficacy and safety were studied in phase II pts and those given RP2S in phase I. In Cohort A-1, for microsatellite stable (MSS) LARC pts, the primary endpoint was centrally confirmed pathologic complete response (pCR) rate using AJCC tumor regression grading. The estimated required sample size assuming null and alternative hypotheses pCR = 10% and 30% was 37 pts, with a 1-sided alpha of 5% and power of 90%. Cohort A-2 was exploratory and included a maximum of 5 MSI-H pts. Results: Nivo 240 mg q2 weeks x 5 cycles, following CRT but pre-S, was the RP2S. From 1/17 to 6/18, 37 pts were enrolled in Cohort A-1. Eleven pts (30%; 90% CI 18-44%) showed pCR (AJCC grade (gr) 0). Including the 3 pts (8%) graded AJCC 1, 14 (38%) had major pathologic responses. In addition, clinical CR was observed in 1 pt (3%) refusing S after nivo. Both MSI-H LARC Cohort A-2 pts showed pCRs. Immune-related severe adverse events were observed in 2 pts (gr 3 myasthenia and gr 2 interstitial nephritis); both fully recovered and had S. No treatment-related deaths were observed. pCR rates of 60% (6/10) and 19% (5/27) (p = 0.038, Fisher exact test) were seen in pts with tumor cells with PD-L1 ≥1% and < 1% IHC staining, respectively, performed on biopsy samples taken pre-CRT. Rates of 62% (8/13) and 10% (1/10) (p = 0.029) were seen in 23 pts with samples analyzable by flow cytometry, according to CD8+ lymphocyte /regulatory T cell (CD8/Treg) ratios ≥2 and < 2, respectively. Conclusions: A promising pCR rate of 30%, with mild toxicity, was shown in MSS LARC pts treated with nivo plus radical S. PD-L1 expression and elevated CD8/Treg ratio may be better predictors of nivo benefit, warranting further study in a larger cohort. Clinical trial information: NCT02948348.

Phase I/II study of neoadjuvant carboplatin, eribulin mesylate, and trastuzumab (ECH) for operable HER2 positive (HER2+) breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS659-TPS659
Author(s):  
Lee Steven Schwartzberg ◽  
Kurt W. Tauer ◽  
Robert C. Hermann ◽  
Petros G. Nikolinakos ◽  
Arthur C. Houts
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Eribulin Mesylate ◽  
Her2 Breast Cancer ◽  
Level 1

TPS659 Background: Carboplatin, docetaxel and trastuzumab (TCH) regimen yields substantial pathologic complete response (pCR) in operable HER2+ breast cancer. Eribulin mesylate (E) is a tubulin inhibitor recently shown to improve overall survival compared to taxanes and other agents in heavily pretreated metastatic breast cancer patients. This trial was designed to determine the maximum tolerated dose (MTD) of E in combination with CH (Phase I) and to determine efficacy and safety of the ECH regimen (Phase II) given as neoadjuvant therapy to early stage HER2+ breast cancer with pathologic complete response the primary endpoint. Methods: This is a multicenter prospective open label single arm trial. Eligible patients were operable stage IIA – IIIB HER2+ breast cancer, ECOG 0-1, normal LVEF, QTc < 480 msec, < grade 1 neuropathy and no history of invasive cancer within the past 3 years. Phase I planned up to 12 patients from 4 centers to 1 of 3 E dose cohorts, with pts treated at the MTD also evaluable for Phase II. Starting dose level 0 was 1.1 mg/m2 with escalation to dose level +1 at 1.4 mg/m2 and de-escalation to dose level -1 at 0.9 mg/m2 if necessary. ECH was given IV for six 3-week cycles with E d1 and d8; C AUC 6 d1; and H 8 mg/kg loading dose d1C1 and 6 mg/kg d1C2-C6. H is scheduled to continue after surgery to complete 1 year of treatment. C1 dose limiting toxicities (DLTs) were defined as: grade 4 thrombocytopenia, anemia, or neutropenia lasting > 5 days; any grade 3-4 non-hematologic toxicity attributable to E, C, H, or the combination; inability to deliver all three agents at assigned dose and schedule. Standard 3+3 dose escalation design was used. At present, 6 patients have been enrolled at dose 0 and 6 have been enrolled at dose +1. The MTD for E has not yet been determined. Phase II has planned enrollment of 44 additional patients from 8 centers with primary endpoint rate of pCR at surgery to be performed 4-8 weeks after completion of ECH and secondary endpoints of safety to include peripheral neuropathy and cardiac toxicity at treatment completion and 1 year follow up. Clinical trial information: NCT101388647.

Phase I/II Trial of Capecitabine, Oxaliplatin, and Radiation for Rectal Cancer

2003 ◽  
Vol 21 (16) ◽  
pp. 3098-3104 ◽  
Author(s):  
Claus Rödel ◽  
Gerhard. G. Grabenbauer ◽  
Thomas Papadopoulos ◽  
Werner Hohenberger ◽  
Hans-Joachim Schmoll ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Sphincter Preservation ◽  
Phase Iii ◽  
Grade 3

Purpose: The purpose of this study was to establish the feasibility and efficacy of preoperative radiotherapy (RT) with concurrent capecitabine and oxaliplatin (XELOX-RT) in patients with rectal cancer. Patients and Methods: Thirty-two patients with locally advanced (T3/T4) or low-lying rectal cancer received preoperative RT (total dose, 50.4 Gy). Capecitabine was administered concurrently at 825 mg/m2 bid on days 1 to 14 and 22 to 35, with oxaliplatin starting at 50 mg/m2 on days 1, 8, 22, and 29 with planned escalation steps of 10 mg/m2. End points of the phase II study included downstaging, histopathologic tumor regression, resectability of T4 disease, and sphincter preservation in patients with low-lying tumors. Results: Dose-limiting grade 3 gastrointestinal toxicity was observed in two of six patients treated with 60 mg/m2 of oxaliplatin. Thus, 50 mg/m2 was the recommended dose for the phase II study. Toxicities observed at this dose level were generally mild, with only two cases of short-lived grade 3 diarrhea. Myelosuppression, mainly leukopenia, was restricted to grade 2 in 19% of patients. T-category downstaging was achieved in 17 (55%) of 31 operated patients, and 68% of patients had negative lymph nodes. Pathologic complete response was found in 19% of the resected specimens. Radical surgery with free margins could be performed in 79% of patients with T4 disease, and 36% of patients with tumors ≤ 2 cm from the dentate line had sphincter-saving surgery. Conclusion: Preoperative XELOX-RT is a feasible and well tolerated treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based therapy with XELOX chemoradiotherapy.

Concurrent chemoradiotherapy with weekly docetaxel and cisplatin for locally advanced head and neck cancer: Phase I study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17026-e17026
Author(s):  
H. S. Kim ◽  
K. Park ◽  
M. J. Ahn ◽  
Y. Park ◽  
S. Lee ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Febrile Neutropenia ◽  
Phase I ◽  
Head And Neck ◽  
Phase I Study ◽  
Locally Advanced ◽  
Maximum Tolerated Dose ◽  
Advanced Head ◽  
Weekly Docetaxel ◽  
Level 3

e17026 Background: This phase I study was performed to determine maximum tolerated dose of docetaxel when administered concomitantly with radiotherapy and cisplatin in patients with locally advanced head and neck cancer. Methods: Fifteen patients were treated at varying levels of docetaxel (level 1: 0 mg/m2, level 2: 10 mg/m2, level 3: 15 mg/m2, and level 4: 20 mg/m2, once per week for a total 6 weeks) with a fixed dose of 20 mg/m2 cisplatin weekly on an outpatient basis. Radiotherapy was delivered as a standard regimen (1.8–2.0 Gy/day, 5 fraction/week) to a total dose of 66–72 Gy. Results: One out of six patients presented with dose-limiting toxicity at the 10 mg/m2/week dose of docetaxel (grade 4 febrile neutropenia which results in treatment-related death). No DLTs was noticed at the 15 mg/m2, and 20 mg/m2 dose level. Thus, the weekly docetaxel dose of 20 mg/m2 was considered as the maximum tolerated dose. Radiotherapy was completed in all patients except one, and more than 95% of the scheduled cisplatin and docetaxel were given in 93% of patients. Acute grade 3–4 toxicities were dominated by anorexia (26.7%), xerostomia (13.3%), and febrile neutropenia (6.6%). Eight (57.1%) and six (42.9%) patients had complete response and partial response. The 2-year actuarial overall survival rate and local control rate were 93.3%, and 87.5%, respectively. With a median 17.5 months (1.25–23.6) of follow-up, 13 out of 14 patients are still alive without evidence of diseases, and only one is alive with evidence of diseases. Conclusions: We determined the MTD of docetaxel to be 20 mg/m2 administered once weekly concurrently with combined with conventionally fractionated RT and weekly 10 mg/m2 CDDP. This chemoradiotherapeutic regimen serves as a promising treatment modality, in which level 3 is the recommended dose for a phase II study. No significant financial relationships to disclose.

A phase I/II multi-center study of nivolumab and carboplatin/paclitaxel with radiation therapy (RT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS199-TPS199
Author(s):  
Iulia Giuroiu ◽  
Geoffrey Yuyat Ku ◽  
Lawrence P. Leichman ◽  
Kevin Lee Du ◽  
Philmo Oh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Clin Oncol ◽  
Phase Ii ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Multi Center Study

TPS199 Background: ESCC comprises 80% of esophageal cancers worldwide. Preoperative chemoRT is a standard-of-care based on the CROSS trial ( N Engl J Med 2012;366:2074-2084), which reported encouraging pathologic complete response (pCR) and overall survival (OS). Surgery is often deferred in patients with clinical CR (cCR) based on lack of overall survival (OS) benefit ( J Clin Oncol 2005;23:2310-2317, J Clin Oncol 2007;25:1160-1168). Nivolumab has activity in advanced ESCC ( Lancet Oncol 2017;18:631-639), and adding it to chemoRT may improve outcomes. ESCC has a high somatic mutation rate and treatment with chemoRT may augment the abscopal effect. Methods: Our trial aims to establish the safety and tolerability (phase I), as well as the efficacy (phase II) of nivolumab added to a standard chemoRT backbone for patients with TanyN1-3 or T3-4N0M0 ESCC. Phase I will enroll up to 12 patients and phase II, up to 44, per an optimal two-stage design. The phase I primary endpoint is unacceptable toxicity at 28 days after the last dose of chemotherapy. Phase II primary endpoints are cCR (endoscopy + PET/CT), pCR for patients undergoing surgery, and median progression-free survival and OS, which will be estimated via Kaplan Meier curves. Extensive tumor and blood immune correlative studies are planned. Clinical trial information: NCT03278626. [Table: see text]

scholarly journals Phase I/II study of sorafenib in combination with erlotinib for recurrent glioblastoma as part of a 3-arm sequential accrual clinical trial: NABTC 05-02

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Huanwen Chen ◽  
John Kuhn ◽  
Kathleen R Lamborn ◽  
Lauren E Abrey ◽  
Lisa M DeAngelis ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Trial Design ◽  
Mapk Pathway ◽  
Maximum Tolerated Dose ◽  
Recurrent Glioblastoma ◽  
Mitogen Activated Protein Kinase ◽  
Grade 3

Abstract Background Receptor tyrosine kinases such as epidermal growth factor receptors (EGFRs) and their downstream signaling pathways such as the Ras-Raf-mitogen-activated protein kinase (MAPK) pathway play important roles in glioblastoma (GBM). This study investigated the safety, pharmacokinetics, and efficacy of sorafenib (Ras/Raf/MAPK inhibitor) in combination with erlotinib (EGFR inhibitor) for treatment of recurrent GBMs. Methods Patients with recurrent GBM were eligible. A novel sequential accrual trial design was used, where patients were sequentially accrued into separate treatment arms in phase I and phase II investigations to optimize recruitment efficiency. In phase I, a standard 3 + 3 format was used to identify dose-limiting toxicities (DLTs), determine maximum tolerated dose (MTD), and investigate pharmacokinetics. Phase II followed a 2-stage design with the primary endpoint being 6-month progression-free survival (PFS6). Results Sixteen patients were recruited for phase I, and the MTD was determined to be sorafenib 200 mg twice daily and erlotinib 100 mg once daily. DLTs include Grade 3 hypertension, Grade 3 elevated liver transaminases, and Grade 4 elevated lipase. While erlotinib did not affect sorafenib levels, sorafenib reduced erlotinib levels. In phase II, 3 of 19 stage 1 participants were progression free at 6 months. This did not meet the predetermined efficacy endpoint, and the trial was terminated. Conclusion This study identified the MTD and DLTs for sorafenib and erlotinib combination therapy for recurrent GBMs; however, efficacy data did not meet the primary endpoint. This study also demonstrates the feasibility of a novel sequential accrual clinical trial design that optimizes patient recruitment for multiarm studies, which is particularly effective for multicenter clinical trials.

FOLFOX and nab-paclitaxel (nab-P) for advanced pancreatic cancer: A phase I study.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 258-258
Author(s):  
Howard Safran ◽  
Kevin Charpentier ◽  
Kimberly Perez ◽  
Kalyan Mantripragada ◽  
Trevor Clark Austin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase I Study ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Maximum Tolerated Dose ◽  
Level 3 ◽  
Grade 3 ◽  
Level 2

258 Background: FOLFIRINOX improves survival in advanced pancreatic cancer, however the contribution of irinotecan is uncertain. The addition of irinotecan to gemcitabine was not superior to gemcitabine alone in pancreatic cancer, however nab-P demonstrates a survival benefit. This phase I study was designed to evaluate the maximum tolerated dose (MTD) of the addition of nab-P to fluorouracil, leucovorin, oxaliplatin (FOLFOX-A). Methods: Patients with metastatic or locally advanced pancreatic adenocarcinoma without prior treatment received oxaliplatin, 85 mg/m2, leucovorin 400 mg/m2 and 5-FU 2400 mg/m2 with 3 dose levels of nab-P (125, 150 and 175 mg/m2) every 2 weeks. Pegfilgrastim was required during the first 2 cycles. Dose limiting toxicities (DLTs) were defined in the first 2 cycles of treatment. Results: Fifteen patients were entered: Dose level 1 (n=6), dose level 2 (N=6), dose level 3 (N=3). The median age was 64 (35-81). Ten patients had metastatic and 5 had locally advanced disease. DLTs of nausea and fatigue occurred in 2 of 3 patients at dose level 3. Two patients developed grade 3 neuropathy after >= 10 cycles of treatment. One patient had grade 3/4 neutropenia. Eight of fifteen patients (53%) had a partial response. Conclusions: The MTD of nab-P is 150mg/m2 every 2 weeks with FOLFOX. Cumulative peripheral neuropathy, similar to other FOLFOX regimens, is the most significant toxicity generally occurring after >= 10 cycles of treatment. FOLFOX-A has substantial activity and may represent a promising regimen in pancreatic cancer. Patients are currently being accrued to an expansion phase utilizing dose level 2. Supported by the Davis and Browning families and LIFEcycle. Clinical trial information: NCT01744353.

Phase I study of preoperative chemoradiation therapy in unresectable locally advanced breast cancer (LABC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11097-11097
Author(s):  
S. Conzen ◽  
O. Hahn ◽  
V. Vanderpuye ◽  
G. Fleming ◽  
F. Olopade ◽  
...  
Keyword(s):  
Phase I ◽  
Locally Advanced Breast Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Stage Iv ◽  
Wound Dehiscence ◽  
Distant Metastases ◽  
Maximum Tolerated Dose ◽  
Prior Chemotherapy

11097 Introduction: Therapy of unresectable LABC is challenging due to the need to resect local disease and prevent distant metastases. We conducted a phase I trial to determine the maximum tolerated dose of preoperative vinorelbine (VIN) combined with paclitaxel (P) and radiation (XRT). Methods: Eligible patients (pts) had unresectable LABC, ECOG performance 0–2 and adequate organ function. Prior chemotherapy and metastatic disease were permitted. All pts received weekly bolus P 80 mg/m2 and concurrent XRT at 2.0 Gy daily for 5 days in a week-on/week-off (WO/WO) schedule for 12 weeks. A planned 59 -70 Gy were delivered to the breast, chest wall and supraclavicular regions. In dose level 2, VIN 15 mg/m2 /week was added. Results: Twenty-six pts were enrolled from July 1999-July 2005 with a median age of 51 years (range 24–69); 9 pts had stage IV disease, 17 pts had stage IIIB disease, and 13 pts had received prior chemotherapy. VIN was not tolerated due to grade (G) 4 neutropenia despite GCSF; however single-agent P and concurrent XRT was well-tolerated. Thus, 7 pts in the final cohort received P/XRT without GCSF. This regimen was well-tolerated; toxicities seen included: G3 in-field skin desquamation 4/7; G4 lymphopenia 7/7, G3 infection 1/7; G3 wound dehiscence 1/7. After therapy, 20/26 pts underwent mastectomy: 6 pts had a pathologic complete response (no invasive disease), 12 had a pathologic partial response (scattered microscopic disease), and 2 pts had no response. Overall pathologic response rate was 90% for pts undergoing mastectomy; only 3 of the 20 resectable pts are alive without relapse a mean of 19.5 months after mastectomy. Conclusions: Neoadjuvant P 80 mg/m2 with full dose XRT in a WO/WO schedule is tolerable and effective allowing 20/26 unresectable pts to undergo successful mastectomy. Pts do not require routine GCSF support. Although most pts eventually relapse distantly, this regimen does render some pts not responding to initial doxorubicin-based therapy resectable. [Table: see text] No significant financial relationships to disclose.

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