Radiotherapy (RT) dose escalation study with concurrent cisplatin and S-1 in patients with inoperable stage III non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7542-7542
Author(s):  
H. Harada ◽  
M. Nishio ◽  
H. Murakami ◽  
F. Ohyanagi ◽  
T. Kozuka ◽  
...  
Keyword(s):  
Radiation Dose ◽  
Febrile Neutropenia ◽  
Organs At Risk ◽  
Performance Status ◽  
Target Volume ◽  
Stage Iii ◽  
Eligibility Criteria ◽  
Metastatic Node ◽  
Dose Escalation Study ◽  
Grade 3

7542 Background: Standard treatment for inoperable stage III NSCLC is concurrent chemoradiotherapy using 3-D conformal RT to a total dose of 60 Gy, but the outcome is still dismal with median survival time (MST) of 16 months and 5-year survival of 15%. We conducted a phase II trial using cisplatin, S-1 and concurrent RT of 60 Gy (J Clin Oncol 2008;26:a7556). MST (33months) was encouraging, however, local failure rate with this trial remained still high. The purpose of this study was to establish the recommended dose (RD) of RT with concurrent cisplatin and S-1. Methods: The eligibility criteria were: histologically or cytologically proven NSCLC, 20–75 years old, performance status 0–1, without any prior chemotherapy or RT. Patients were treated with cisplatin (60 mg/m2 on day 1) and S-1 (orally at 40 mg/m2/dose b.i.d., on days 1–14) repeated every 4 weeks for 4 cycles and RT was started on day 1. Radiation dose was escalated from 66 Gy in 33 fractions (Arm 1) to 70 Gy in 35 fractions (Arm 2), then 74 Gy in 37 fractions (Arm 3). The dose was to be escalated if DLTs were observed in 2 or less patients. The target volume of RT included primary tumor and metastatic node only and elective nodal irradiation was not performed. Dose constraints to the organs at risk were: the lung, V20 < 30%; the esophagus, mean dose < 34 Gy and V55 < 30%; the spinal cord, max dose < 50 Gy. Results: Six patients in each arm were enrolled. Two patients in Arm 1 experienced DLTs: one patient developed grade 3 febrile neutropenia, grade 3 mucositis in oral cavity and grade 3 diarrhea and one patient developed grade 3 febrile neutropenia. One patient in Arm 3 has not been completed evaluation yet. Otherwise no DLT was observed. Conclusions: The radiation dose of 74 Gy in 37 fractions with concurrent cisplatin and S-1 seemed to be tolerable and was judged to be the RD. This study is still open to accrue another six patients to confirm the safety of the RD. No significant financial relationships to disclose.

A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (pts) with stage III A/B non-small cell lung cancer (NSCLC): An interim report of the RTOG 0324 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7531-7531 ◽  
Author(s):  
G. Blumenschein ◽  
J. Moughan ◽  
W. Curran ◽  
F. Robert ◽  
F. Fossella ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Pulmonary Complications ◽  
Model Systems ◽  
Stage Iii ◽  
Preclinical Model ◽  
Eligibility Criteria ◽  
Trial Testing ◽  
Grade 3

7531 Background: Cetuximab (C225) is a chimerized monoclonal antibody that targets the epidermal growth factor receptor (EGFR). NSCLC commonly expresses the EGFR, which is associated with aggressive tumor behavior and poor clinical outcome. Preclinical model systems demonstrate radiosensitization following molecular inhibition of EGFR signaling. Methods: We report a phase II trial testing the combination of C225 with CRT in unresectable stage III NSCLC with a planned sample size of 84 PTS. Eligibility criteria included Zubrod performance status (PS) = 1, weight loss = 5% over past 3 months, FEV1 = 1.2 l, adequate hematologic, hepatic, and renal function. PTS received an initial dose of C225 (400 mg/m2) on day 1 of week 1, then weekly doses of C225 (250 mg/m2) until completion of therapy (weeks 2 –17). During week 2, patients started CRT (63 Gy/35 fractions) with weekly carboplatin (C) AUC 2 and paclitaxel (P) 45 mg/m2 × 6 doses followed by C (AUC 6) and P (200 mg/m2) × 2 cycles (weeks 12–17). Interim monitoring for severe (grade = 3) or excessive non-hematologic toxicities occurred after pts had been treated and followed for at least 90 days after RT. Primary endpoints include safety and compliance of concurrent C225 and CRT. Results: 93 pts were enrolled with 87 evaluable pts. Pts characteristics: 57% male, median age 64 years (range 42–85), 47% PS 0, 46% stage IIIA. Median follow-up is 14 months. Response rate is 62% (n=54) and 12 month overall survival (OS) is 68% (# at risk=56). Adverse events related to treatment include 20% (n=17) of pts with grade 4 hematologic toxicities and 7 pts who had grade 3 esophagitis. There was 1 infection related death, 1 death NOS, and 3 pts who died of pulmonary complications (adult respiratory distress syndrome, pneumonitis, and hypoxia). Conclusions: The combination of C225 with CRT is feasible. Further study will be needed to determine whether the addition C225 to CRT enhances toxicity or efficacy. Complete compliance and toxicity data along with 18 month OS will be reported. No significant financial relationships to disclose.

A Phase II Study of S-1 for Previously Untreated Elderly Patients with Advanced Non-Small Cell Lung Cancer

Chemotherapy ◽  
2015 ◽  
Vol 61 (2) ◽  
pp. 93-98 ◽  
Author(s):  
Takashi Kasai ◽  
Yoichi Nakamura ◽  
Minoru Fukuda ◽  
Takeshi Kitazaki ◽  
Seiji Nagashima ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Elderly Patients ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
Eligibility Criteria ◽  
Grade 3

Background: S-1, a novel oral fluoropyrimidine, is active in the treatment of non-small cell lung cancer (NSCLC). However, data on S-1 for elderly patients with NSCLC are insufficient. Methods: Eligibility criteria were no prior chemotherapy, stage IIIB or IV NSCLC, performance status 0-1, age >70 years, and adequate hematological, hepatic, and renal functions. Patients received S-1 (40 mg/m2 twice a day) for 28 consecutive days. This schedule was repeated every 6 weeks. The primary end point was the tumor response rate. Results: Thirty-two patients were enrolled and 31 patients were evaluable for response. The patients' median age was 80 years (range: 71-88). The response rate was 22.6% (95% CI: 11-38). Neutropenia, anemia, thrombocytopenia, febrile neutropenia, and diarrhea of grade ≥3 occurred in 6, 6, 10, 3, and 3%, respectively. Conclusions: In elderly patients with previously untreated advanced NSCLC, S-1 appears to be well tolerated and demonstrates encouraging activity.

A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated, Stage III or IV, Low-Grade B-Cell Non-Hodgkin’s Lymphoma (NHL) or Bulky Stage II Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1354-1354
Author(s):  
Raul R. Mena ◽  
Neil P. Christiansen ◽  
Yudhishtra Markan ◽  
Lalita Pandit
Keyword(s):  
Febrile Neutropenia ◽  
B Cell ◽  
Single Agent ◽  
Stage Ii ◽  
Stage Iii ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Purine Analog ◽  
Previously Treated ◽  
Grade 3

Abstract The decision to treat indolent B-cell NHL is often based on progression of the disease. Most regimens have utilized fludarabine as the purine analog but the myelosuppression and immunosuppression of fludarabine combinations frequently results in severe infections. Combination therapy with pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody, based on the single-agent activities, documented synergy, and non-overlapping toxicity profiles, may represent a promising approach in the treatment of these patients. To further investigate the efficacy of the PCR regimen for the treatment of indolent NHL, we conducted a phase II study. Patients diagnosed of bulky stage II, stage III/IV low-grade NHL (REAL classification), previously untreated or treated, were eligible. All patients were treated with intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for at least 8 cycles. 2 additional cycles were given for patients with PR or SD after cycle 8 or patients with CR/CRu first evident at cycle 8. Clinical evaluation was performed after cycles 2, 4, 6, 8, and 10 if necessary. Dose modification for hematologic toxicity may be increased to the previous higher level when a hematologic toxicity returned to normal. Two 25% dose reductions or one 50% dose reduction were allowed for nonhematologic toxicity. One hundred patients with indolent NHL, 68 previously untreated, 26 previously treated, and 6 with unknown treatment history, were enrolled in the study. The median age was 61 years (range 29–84) and 63.4% were ECOG PS 0, 36.6% PS1. A total of 550 cycles were given, with a median of 6 cycles per patient. 8 patients were not evaluated for response due to withdrawal of consent (n=1), unacceptable toxicities (n=3), and missing data (n=4). 92 patients received at least two cycles of treatment and were evaluated for response. The highest response rate (RR) achieved was 68%, with 10 (10%) CR, 12 (12%) CRu, 46 (46%) PR, 23 (23%) SD, and 1 (1%) disease progression. Stratified according to previous treatment status, patients with previously untreated NHL had an RR of 47% (CR, CRu 17%) while that of the previously treated was 17% (CR 7%). 14 (14.0%) patients discontinued treatment due to toxicities. Grade 3/ 4 hematological adverse events documented included 10 grade 4 and 16 grade 3 neutropenia. Infectious complications were noted in 8 patients including 3 grade 3 febrile neutropenia, 2 grade 4 febrile neutropenia, and 3 grade 3 infections. A total of 4 deaths were recorded, including 1 due to acute myocardial infarction, 1 suspected cardiac event and 2 unknown causes. This immunochemotherapeutic regimen is active in patients with indolent NHL. The study is currently on-going and updated results will be presented.

A phase III study of Æ-941 with induction chemotherapy (IC) and concomitant chemoradiotherapy (CRT) for stage III non- small cell lung cancer (NSCLC) (NCI T99–0046, RTOG 02–70, MDA 99–303)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7527-7527 ◽  
Author(s):  
C. Lu ◽  
J. J. Lee ◽  
R. Komaki ◽  
R. S. Herbst ◽  
W. K. Evans ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Performance Status ◽  
Stage Iiib ◽  
Phase Iii ◽  
Stage Iii ◽  
Type I ◽  
Eligibility Criteria ◽  
Unresectable Stage ◽  
Significant Difference ◽  
Stage Iii Nsclc

7527 Background: Æ-941 is a shark cartilage extract with antiangiogenic properties. We conducted a placebo-controlled trial testing Æ-941, with IC and CRT, in unresectable stage III NSCLC. Methods: Eligibility criteria included performance status (PS) < 2, weight loss < 10%. Subjects received one of two treatment regimens depending on site of enrollment: carboplatin (C) (AUC 6) and paclitaxel (P) (200 mg/m2) × 2 cycles followed by CRT (60 Gy/30 fractions) with weekly C (AUC 2) and P (45 mg/m2) × 6 doses or cisplatin (CDDP) (75 mg/m2, d1) and vinorelbine (V) (30 mg/m2, d1 and 8) × 2 cycles followed by CRT (60 Gy/30 fractions) with CDDP (75 mg/m2, day 1) and V (15 mg/m2, d1 and 8) × 2 cycles. Subjects were randomized to receive Æ-941 (Arm A) or placebo (Arm B), 120 mL orally twice daily, at the start of IC and continuing after CRT as maintenance therapy. Randomization was stratified for stage, gender, and type of chemotherapy. The primary endpoint was overall survival (OS), with a planned sample size of 756 subjects providing 80% power to detect a 25% difference in OS, assuming a control arm median survival time (MST) of 13 months, type I error 0.05. Results: Between 6/00 and 2/06, 384 subjects were enrolled onto the trial and randomized. In 2/06 the trial was closed to new patient entry due to insufficient accrual. This final analysis is based on 379 randomized and eligible subjects (188 arm A, 191 arm B). Subject characteristics: 60% male, median age 63 years (range 37–84), 56% stage IIIB, 58% C-based chemotherapy, median follow-up 3.7 years. There was no significant difference in OS between arms A and B, with MSTs of 14.4 (95% CI 12.6–17.9) and 15.6 (95% CI 13.8–18.1) months, respectively (log-rank p=0.73). OS by pre-specified stratification factors: stage IIIB vs IIIA (MST 13.9 vs. 17.4 months, p=0.25), C vs. CDDP chemotherapy (MST 14.4 vs. 16.7 months, p=0.13), and male vs. female (MST 15.7 vs. 15.1 months, p=0.74). The study drug was well tolerated. Fewer subjects in arm A experienced grade 3 or higher adverse events (66% vs. 77%, p=0.018). Conclusions: The addition of Æ−941 to IC and CRT does not improve OS in patients with unresectable stage III NSCLC. No significant financial relationships to disclose.

Phase II study of gemcitabine, oxaliplatin in combination with bevacizumab (GEMOX-B) in patients with unresectable or metastatic biliary tract and gallbladder cancers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4625-4625 ◽  
Author(s):  
J. W. Clark ◽  
J. A. Meyerhardt ◽  
D. V. Sahani ◽  
S. Namasivayam ◽  
T. A. Abrams ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Fdg Pet ◽  
Poor Prognosis ◽  
Performance Status ◽  
Progression Free Survival ◽  
Whole Body ◽  
Eligibility Criteria ◽  
Tract Cancer ◽  
Clinically Significant ◽  
Grade 3

4625 Background: Patients (Pts) with unresectable or metastatic biliary tract cancer (BTC) and gallbladder cancer (GBC) have a poor prognosis. Vascular endothelial growth factor (VEGF) expression has been detected in BTC and GBC. Increased angiogenesis has been correlated with advanced stage of disease and poor prognosis. Given reported activity of gemcitabine (GEM) and oxaliplatin (OX) in BTC/GBC and potential benefits of targeting the VEGF pathway with bevacizumab (B), we performed a study to examine the efficacy and tolerability of GEM, OX and B (GEMOX-B) in unresectable or metastatic BTC/GBC. Methods: Eligibility criteria included unresectable or metastatic measurable BTC/GBC, 0–1 prior chemotherapy regimens, performance status = 2, and adequate organ function. No clinically significant cardiovascular disease or history of active bleeding. Pts were treated with all 3 drugs intravenously on days 1 and 15 every 28 days (one cycle): B was given first at 10 mg/kg, followed by GEM at 1000 mg/m2 as dose rate infusion at 10 mg/m2/minute, and OX at 85 mg/m2. Whole body FDG-PET scan was obtained at baseline and after cycle 2. The primary endpoint of the study was progression-free survival (PFS). Results: 19 pts (10 BTC and 9 GBC) have been enrolled since May 17, 2006: median age = 69 (25–82), M/F = 13/6, ECOG 0/1/2 = 7/10/2. Treatment has been well tolerated with no grade 4–5 toxicities seen. Treatment related grade 3 toxicities included (number of pts): hypertension (2), neutropenia (1), transient SGPT elevation (1), proteinuria (1), neuropathy (1), and fatigue (1). Of 11 pts followed for at least 4 months, 3 had confirmed partial responses (PR), 5 had stable disease (SD) of at least 4 cycles, and 3 had progressive disease (PD) per RECIST criteria. Five pts had more than 50% decrease in CA19–9 levels. Of 16 PET studies analyzed, changes in SUV values from baseline to after 2 cycles of treatment were: 11 PRs, 4 SDs, 1 PD per EORTC criteria. Conclusions: GEMOX-B can be safely administered with tolerable safety profiles in patients with advanced BTC/GBC. Early evidence of antitumor activity was seen. A decreased SUV in FDG-PET following GEMOX-B treatment was observed in the majority of patients. No significant financial relationships to disclose.

Phase II study of TS-1 (S) plus cisplatin (P) with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18070-18070
Author(s):  
F. Ohyanagi ◽  
N. Yamamoto ◽  
A. Horiike ◽  
T. Horai ◽  
K. Gomi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Fourth Generation ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3

18070 Background: Although combined chemoradiotherapy is the standard of care in stage III NSCLC, the optimal chemotherapy regimen is not established. S-1, a fourth-generation oral fluoropyrimidine is an active new agent for NSCLC and the combination with cisplatin has a favorable toxicity profile. The objective of this study was to evaluate feasibility and efficacy of S plus P with concurrent radiation for unresectable stage III NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC, 20 to 75 years in age, performance status 0–1, with no prior chemotherapy were eligible for the study. Patients were treated with P (60 mg/m2 on day 1) and S (orally at 40 mg/m2/dose bid (80 mg/m2/d), on days 1 to 14) repeated every 3–4 weeks for 4 cycles and TRT (60 Gy/30 fr over 6 weeks starting on day 2). The primary endpoint was the response rate (RR), and planned sample size for this phase II study was 28 patients (Simon’s two-stage minimax design, P0=70%, P1=90%, a =0.1, β = 0.1). Results: Of 28 patients enrolled between August 2005 and October 2006, 28 were evaluable. There were 24 males and 4 females, median age of 63 (range 40–74) and 11 IIIA and 17 IIIB. Chemoradiotherapy was well tolerated; 2 cycles of SP and 60 Gy of TRT were administered in all patients and 24 (86%) patients received 4 cycles of SP. During concurrent chemoradiotherapy, grade 3 toxicities were neutropenia (8 pts), leukopenia (6 pts), fatigue (6 pts), anorexia (5 pts), febrile neutropenia (4 pts) and, esophagitis (4 pts). Only one grade 4 leukopenia were observed. During consolidation therapy, grade 3–4 neutropenia, anemia, esophagitis, and pneumonitis were developed in 4, 1, 1 and 2 patients, respectively. No toxic deaths have occurred. Overall RR was 85.7% (95% CI: 79.1- 98.7%) with 4 SDs and 24 PRs. The median progression-free survival and median survival is not mature enough to estimate as only 4 progression and no deaths have occurred. Conclusions: This chemoradiotherapy regimen produced promising response rate in patients with stage III NSCLC and it seems to be well-tolerated. No significant financial relationships to disclose.

A phase I study of brostallicin (B) combined with either bevacizumab (BV) or irinotecan (I) in patients (pts) with advanced solid malignancies

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13531-e13531
Author(s):  
R. B. MacArthur ◽  
J. Singer ◽  
C. Becerra ◽  
S. Weitman ◽  
D. Von Hoff
Keyword(s):  
Febrile Neutropenia ◽  
Phase I ◽  
Solid Tumors ◽  
Performance Status ◽  
Single Agent ◽  
Primary Objective ◽  
Additional Patient ◽  
Dna Minor Groove ◽  
Grade 3 ◽  
Group Grade

e13531 Background: B is a DNA minor groove binding (MGB) agent with single agent cytotoxic activity. B has shown synergy with BV and I. The combinations were studied using a “complete” phase I design. Methods: The primary objective was to determine the maximally tolerated dose (MTD) and dose limiting toxicities (DLT) of B+BV and B+I. For B+BV cohort 1 both drugs were infused on day 1 of a 21 day cycle. BV was dosed at 15mg/kg, B was dosed at 6 mg/m2. For cohort 2, the BV dose was unchanged, and B dose reduced to 4 mg/m2. For B+I cohort 1 both drugs were also infused on cycle day 1. I was dosed at 200 mg/m2 with B at 4 mg/m2. For cohort 2, I was reduced to 125 mg/m2 and B reduced to 2 mg/m2. Cycle 1 DLT was defined: grade 4 neutropenia lasting ≥ 5 days, grade 3 or higher febrile neutropenia, grade 4 thrombocytopenia or grade 3 or 4 thrombocytopenia with bleeding, grade 3 or higher diarrhea, nausea or vomiting despite optimal management, grade 3 or higher for all other non-hematologic toxicities. For pts receiving BV, grade 2 or higher proteinuria. Eligible pts had treatment refractory metastatic/unresectable solid tumors, acceptable performance status, and adequate hematologic parameters and organ function. Results: 19 pts were enrolled. 11 pts received B+BV and 8 received B+I. Median age was 58 years. For B+BV 5 patients were treated in cohort 1, 6 in cohort 2. For B+I, 2 patients were treated in cohort 1, 6 in cohort 2. The MTD has not been defined for either treatment combination. In the current preliminary dataset 18/19 pts (93.3%) experienced one or more adverse events (AEs). In the B+BV group, grade 4 neutropenia was reported in 2/11 patients, both in cohort 1, and grade 3 neutropenia in one additional patient, also in cohort 1. In the B+I group, grade 4 AEs included neutropenia (DLT), febrile neutropenia (DLT), severe abdominal pain, and thrombocytopenia. Of the evaluable pts, no complete or partial responses were seen. For B+BV 5/11 pts have received 4 or more cycles, and for B+I 2/8. Conclusions: The combination of B+BV and B+I show manageable toxicity in advanced solid tumors at the doses reached in cohort 2. Additional data will be provided at the time of presentation. [Table: see text]

Phase Ib study of RG7112 with doxorubicin (D) in advanced soft tissue sarcoma (ASTS).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10514-10514 ◽  
Author(s):  
Sant P. Chawla ◽  
Jean-Yves Blay ◽  
Antoine Italiano ◽  
Martin Gutierrez ◽  
Axel Le Cesne ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Febrile Neutropenia ◽  
Single Agent ◽  
Safety Data ◽  
High Rate ◽  
Preliminary Review ◽  
Dose Escalation Study ◽  
Combination Methods ◽  
P53 Activation ◽  
Grade 3

10514 Background: Preclinical data demonstrate p53-dependent MIC-1 activation by both D and the MDM2 inhibitor RG7112. This study evaluated the tolerability of combining D with RG7112 in ASTS patients (pts) and pharmacokinetic (PK) and pharmacodynamic (PD) parameters of the combination. Methods: A phase 1b 3+3 dose escalation study was designed. Pts with ASTS in whom D was considered appropriate were eligible. D was administered IV at either 50 mg/m2 or 60 mg/m2on day 1 with RG7112 administered orally 500 or 1000 mg QD for 3 or 5 days (d1-3 or d1-5) in 28-d treatment cycles. Safety, PK and PD, including serum MIC-1 (an indicator of p53 activation), were assessed. Results: As of January 15, 2013, enrollment was complete with 23 pts with ASTS accrued; safety data for cycle 1 was available for preliminary review in 20 pts. Growth factor support was mandated following the first dosing group (D 60 mg/m2and RG7112 500 mg x 5d) due to febrile neutropenia or grade 4 neutropenia. Of the 20 pts for which cycle 1 safety data is available, 13 pts reported neutropenia (12 grade 3/4); 5 reported grade 3/4 febrile neutropenia (3 following mandatory GCSF prophylaxis); 12 pts developed thrombocytopenia (9 grade 3/4). PK parameters of the combination therapy are similar to single agent values and did not demonstrate evidence of drug-drug interactions. Serum MIC-1 rapidly increased to levels greater than for either agent alone. Best response to date is stable disease in 8/16 pts who have had interim evaluations. Conclusions: Combination therapy with D and RG7112 resulted in a high rate of grade 3/4 neutropenia (60%) or thrombocytopenia (45%). PK analysis does not suggest this is due to changes in the metabolism of either drug. This combination demonstrates apparent potentiation of p53 activation demonstrated by increased MIC-1 levels greater than additive effects of the single agents. Biomarker analyses, safety, PK, and MIC-1 data will be presented. Clinical trial information: NCT01605526. [Table: see text]

Investigation of the tolerability of FOLFIRINOX in patients with unresectable advanced pancreatic cancer: Single-institution experience in Japan.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 487-487 ◽  
Author(s):  
Kouichirou Miyashita ◽  
Takashi Sekikawa ◽  
Ken Shimada ◽  
Taikan Yamamoto ◽  
Yasuhiro Kaga ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Practice ◽  
Clinical Stage ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Dose Intensity ◽  
Eligibility Criteria ◽  
Grade 3 ◽  
Practice Methods

487 Background: FOLFIRINOX therapy has contributed to the overall survival extension of unresectable advanced pancreatic cancer. This regimen is however associated with significant toxicity. And doing the treatment, while careful to toxicity at our institution. We investigated the tolerability of FOLFIRINOX for the treatment of unresectable advanced pancreatic cancer in clinical practice. Methods: We conducted a retrospective analysis of patients with unresectable advanced pancreatic cancer who received FOLFIRINOX between November 2012 and August 2014. FOLFIRINOX is as follows: irinotecan at 150 mg/m2; oxaliplatin at 85 mg/m2; 5-fluorouracil (5FU) at 400mg/m2 bolus, 2,400mg/m2 continuous infusion. Patients' characteristics, objective response, survival and toxicities were collected. Response were evaluated with RECIST version 1.1 and toxicities with NCI-CTCAE version 4.0. Results: 13 patients were includes (8 males and 5 females). Treatment eligibility criteria in our institution were Performance Status 0 or 1, and UGT1A1 polymorphisms were excluded. Median age was 58.6 years (41-74). Clinical stage IVa/IVb was 3/10. The mean number therapy was 7.7 (3-15) cycles. The toxicity of all grade was 100% and grade 3 was 80%. The non-hematological toxicities included nausea in 8 patients (61.5%) and anorexia in 9 (69.2%). The hematological toxicities included neutropenia in 12 patients (92.3%), of which 11 (84.6%) presented a grade 3/4 neutropenia. In patients who developed grade 3 neutropenia, the treatment of FOLFIRINOX could be continued once every three weeks (triweekly) without reducing the dose. Response rate was 38.5% (CR: 0, PR: 5, SD: 6, PD: 2) and disease control rate was 84.6%. Time to treatment failure was 175 days. Relative dose intensity was 95.0% for oxaliplatin, 88.9% for irinotecan, 81.9% for 5FU (bolus), and 95.6% for 5FU (continuous). Conclusions: In clinical practice, it is expected that FOLFIRINOX is an effective, well-tolerated regimen by reducing the dose or determining the appropriate dosing interval.

scholarly journals Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non–Small-Cell Lung Cancer

2020 ◽  
Vol 38 (7) ◽  
pp. 706-714 ◽  
Author(s):  
Jeffrey D. Bradley ◽  
Chen Hu ◽  
Ritsuko R. Komaki ◽  
Gregory A. Masters ◽  
George R. Blumenschein ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Dose ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Concurrent Chemotherapy ◽  
Small Cell ◽  
Stage Iii ◽  
High Dose ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non–small-cell lung cancer (NSCLC). METHODS The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS). RESULTS Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm v 12.1% and 17.4% in the HD arm, respectively ( P = .0005 and < .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7 v 20.3 months ( P = .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% ( P = .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms. CONCLUSION A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.

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