Efficacy and safety of bevacizumab (BEV)-based combination regimens in patients with metastatic colorectal cancer (mCRC): Randomized phase II study of BEV + FOLFIRI versus BEV + XELIRI (FNCLCC ACCORD 13/0503 study)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4086-4086
Author(s):  
M. Ducreux ◽  
A. Adenis ◽  
J. Mendiboure ◽  
E. François ◽  
E. Boucher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Ecog Performance Status ◽  
Free Survival ◽  
First Line Therapy ◽  
Number Of Cycles ◽  
Combination Regimens

4086 Background: The combination of BEV and chemotherapy is highly effective in patients with mCRC and improves response rate, progression-free survival and overall survival compared with chemotherapy alone. This randomized non-comparative phase II trial evaluated the efficacy and safety of BEV in combination with either XELIRI or FOLFIRI as first-line therapy for mCRC. Methods: Patients were eligible for inclusion in this study if they had histologically proven measurable mCRC, were aged 18–75 years, and had an ECOG performance status (PS) of 0–2. Patients were treated with 8 cycles of XELIRI (irinotecan 200 mg/m2 on Day 1 and capecitabine 1000 mg/m2 bid on Days 1–14) + BEV 7.5 mg/kg on Day 1, every 3 weeks or 12 cycles of FOLFIRI (irinotecan 200 mg/m2 on Day 1 + 5-fluorouracil (5-FU) 400 mg/m2 + folinic acid 400 mg/m2 on day 1 followed by 5-FU 2400 mg/m2 via 46-h infusion) + BEV 5 mg/kg on day 1, every 2 weeks. BEV was continued to disease progression. Patients aged ≥65 years received a lower daily dose of capecitabine (800 mg/m2 bid). The primary endpoint was crude progression-free survival (PFS) at 6 months. Results: In total, 145 patients were entered in the study between March 2006 and January 2008; 72 patients received BEV + XELIRI and 73 patients received BEV + FOLFIRI (male 64%/48%; median age 61/61 years; 35/36% aged >65 years). Preliminary results from the first 6 months of follow-up are reported here. A total of 491/783 cycles was administered, 63%/67% receiving at least the initially planned number of cycles (8 cycles for BEV + XELIRI and 12 for BEV + FOLFIRI). Main results are given in the table . Conclusions: This randomized non-comparative study has shown that BEV + XELIRI and BEV + FOLFIRI are similarly effective treatments for patients with mCRC, with manageable toxicity profiles. Results with updated follow-up will be presented at the Meeting. [Table: see text] [Table: see text]

Phase II efficacy and safety study of nintedanib versus sunitinib in previously untreated renal cell carcinoma (RCC) patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4506-4506 ◽  
Author(s):  
Tim Eisen ◽  
Yaroslav Shparyk ◽  
Robert Jones ◽  
Nicholas James MacLeod ◽  
Graham Temple ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Qtc Interval ◽  
Efficacy And Safety ◽  
Ecog Performance Status ◽  
Interval Change ◽  
First Line Therapy

4506 Background: Sunitinib (S) is established as a standard first-line therapy for patients (pts) with advanced RCC. However, treatment can be limited by the occurrence of drug-related adverse events (AEs). This Phase II study assessed the efficacy and safety of nintedanib (N) – a potent, triple angiokinase inhibitor of VEGFR-1–3, PDGFR-α/β, and FGFR-1–3, as well as RET and Flt3 – vs S in previously untreated pts with RCC. Methods: Ninety-nine eligible pts (96 of whom were treated) with advanced, unresectable/recurrent clear cell RCC, an ECOG performance status of 0–1, and no prior systemic therapy were randomized 2:1 to receive N 200 mg twice daily (n=64; given in 4-week cycles) or S 50 mg once daily (n=32; 4 weeks on, 2 weeks off schedule). Treatment continued until disease progression or unacceptable drug-related AEs. Primary endpoints were progression-free survival at 9 months (PFS-9) and, in N-treated pts only, QTc interval change (baseline to day 15). Secondary endpoints included PFS, objective response rate (ORR; RECIST 1.1), overall survival (OS), time to progression (TTP), time to treatment failure (TTF), and AEs. Results: Baseline characteristics were balanced between the arms. PFS-9 was not statistically significantly different between N- and S-treated pts (43 vs 45%; p=0.85). There were also no statistically significant differences between N and S with regard to PFS (median: 8.44 vs 8.38 mo; hazard ratio: 1.16; 95% CI: 0.71–1.89; p=0.56), confirmed ORR (18.8 vs 31.3%; p=0.19), OS (median: 20.37 vs 21.22 mo; p=0.63), TTP (median: 8.48 vs 8.54 mo; p=0.52), and TTF (median: 8.41 vs 8.36 mo; p=0.46). Grade ≥3 AEs occurred in 47% of N-treated pts and 56% of S-treated pts. Common AEs (all grades; N vs S) included diarrhea (61 vs 50%), nausea (38 vs 34%), fatigue (both 25%), and vomiting (16 vs 22%). Dermatologic AEs (8 vs 47%) were less frequent with N than S. There was no increase from baseline in QTc >60 ms on days 1 or 15 in N-treated pts, and there was no relationship between N exposure and QT interval change. Conclusions: N demonstrated similar efficacy to S and had a manageable safety profile, including a lower incidence of dermatologic AEs vs S. In addition, N was not associated with QT prolongation. Clinical trial information: NCT01024920.

scholarly journals Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew J. Brenner ◽  
John Floyd ◽  
Lisa Fichtel ◽  
Joel Michalek ◽  
Kunal P. Kanakia ◽  
...  
Keyword(s):  
Median Time ◽  
Phase Ii ◽  
Phase 1 ◽  
Performance Status ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Time To Death ◽  
Phase 2 Trial

AbstractEvofosfamide (Evo or TH302) is a hypoxia-activated prodrug which is reduced leading to the release of alkylating agent bromo-isophosphoramide mustard, which has shown safety and signals of efficacy in a prior phase 1 study in recurrent glioblastoma. We performed a dual center single-arm Phase II study to expand on the safety and efficacy of Evo plus bevacizumab in bevacizumab refractory glioblastoma. 33 patients with bevacizumab refractory GBM received Evo 670 mg/m2 in combination with Bevacizumab 10 mg/kg IV every 2 weeks. Assessments included adverse events, response, and survival. Median age of patients was 47 (range 19–76) and 24 (69%) were male. At the time of study entry, 9 (26%) had ongoing corticosteroid use. ECOG performance status was 0 or 1 in 83% of patients. Patients were mostly heavily pretreated with 77% have three or more prior regimens. A total of 12 patients (36%) suffered grade 3–4 drug associated adverse event (AE); no grade 5 AE were reported. Of the 33 evaluable patients, best response was PR in 3 (9%), SD in 14 (43%), and PD in 16 (48%) with responses confirmed by a second reviewer. Median time to progression of disease was 53 days (95% CI 42–113) and Median time to death was 129 days (95% CI 86–199 days). Progression free survival at 4 months (PFS-4) on Evo-Bev was 31%, which was a statistically significant improvement over the historical rate of 3%. The median overall survival of patients receiving Evo-Bevacizumab was 4.6 months (95% CI 2.9–6.6). The progression free survival of patients on Evo-Bevacizumab met the primary endpoint of progression free survival at 4 months of 31%, although the clinical significance of this may be limited. Given the patient population and Phase II design, these clinical outcomes will need further validation.

Phase II study of S-1, oral leucovorin, oxaliplatin, and bevacizumab combination therapy (SOL+BV; SOLA) in patients with unresectable metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 611-611 ◽  
Author(s):  
Takeshi Kato ◽  
Tomohiro Nishina ◽  
Kentaro Yamazaki ◽  
Takayuki Yoshino ◽  
Yoshinori Miyata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Regression ◽  
Performance Status ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Prolonged Treatment ◽  
Efficacy And Safety ◽  
Resection Rate ◽  
Ecog Performance Status ◽  
Grade 3

611 Background: The results from a randomized phase II trial in the first-line treatment of mCRC indicated that SOL regimen (S-1, Oral Leucovorin; LV, and Oxaliplatin) had promising activity with well-tolerated toxicities compared to mFOLFOX6 (Ojima et al, ESMO 2011). The median progression-free survival (PFS) for SOL and mFOLFOX6 was 9.6 and 6.9 months, respectively (HR=0.83). We evaluated the efficacy and safety of adding BV to SOL regimen in this study. Methods: The inclusion criteria were; 1) histologically proven adenocarcinoma of colon or rectum, 2) age ≥ 20 years, 3) no prior treatment for metastatic disease, 4) at least one target lesion by RECIST ver1.0 criteria, 5) ECOG Performance Status 0-1. Patients (pts) received S-1 (40-60 mg bid) and LV (25 mg bid) orally for one week and L-OHP (85 mg/m2), and BV (5 mg/kg) on day 1, every 2 weeks. The primary endpoint was the response rate (RR). Results: From October 2009 to April 2010, 31 pts were enrolled, and 29 pts were regarded as the population of full analysis set. Present data included the results of efficacy and safety up to 24 cycles. RR assessed by the independent review committee was 86.2 % (CR: 0 pts, PR: 25 pts), and disease control rate (DCR) was 100%. The median PFS assessed by investigators was 12.5 months, while further follow up is ongoing. One year survival rate was 100%. The incidence of grade 3/4 adverse drug reactions were; neutropenia 16.7%, diarrhea 10.0%, hypertension 16.7%, and sensory neuropathy 53.3%. The median cumulative oxaliplatin dose was 915.0 mg/m2 (range 330-1735 mg/m2). The high prevalence of grade 3 neuropathy seemed due to the prolonged treatment duration. Reasons for discontinuation were progressive disease in 13 pts, and metastatectomy by tumor regression in 6 pts. The resection rate was 17.2 %. Conclusions: SOL+BV showed promising activity with high RR, DCR, PFS and resection rate with well tolerated toxicities in pts with unresectable mCRC. This trial was supported by Taiho Pharmaceutical CO.,LTD. (JAPIC Clinical Trials information Identifier: JapicCTI-090881).

Predictive value of BRCA1, ERCC1, ATP7B, PKM2, TOPO-I, TOPO-iia, TOPO-iib, and c-MYC genes in patients with small cell lung cancer (SCLC) who received first-line therapy with cisplatin and etoposide.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7594-7594
Author(s):  
Chara Papadaki ◽  
Niki Karachaliou ◽  
Eleni Lagoudaki ◽  
Maria Trypaki ◽  
Maria Sfakianaki ◽  
...  
Keyword(s):  
Predictive Value ◽  
Performance Status ◽  
Progression Free Survival ◽  
University Hospital ◽  
Integrated Analysis ◽  
Ecog Performance Status ◽  
Primary Tumors ◽  
Free Survival ◽  
First Line Therapy ◽  
The University

7594 Background: to evaluate the predictive value of genes correlated with cisplatin-etoposide (EP) metabolism or mode of function in patients with SCLC. Methods: Tumor samples from 184 patients, with SCLC were analyzed for ERCCI, BRCA1, ATP7B, TOPOI, TOPOIIA, TOPOIIB PKM2 and C-MYC mRNA expression by quantitative real-time PCR, from microdissected cells derived from patients’ primary tumors. All patients were treated with EP (plus radiotherapy for patients with limited disease-LS) in the department of Medical Oncology of the University Hospital of Heraklion. Results: The median age of the patients was 63 years (min-max: 33-78). One hundred-twenty (65%) patients presented with extended stage (ES), LDH was above the UNL in 75 (41%), while ECOG performance status was 0-1 in 131 (71%) of them. Shorter progression free survival (PFS) was observed in patients with LS-SCLC whose tumors expressed high ERCC1 (p=0.028), PKM2 (p=0.046), TOPO-I (p=0.008), TOPO-IIA (p=0.002) and TOPO-IIB (p<0.001) expression. High expression of ERCC1 (p=0.014), PKM2 (p=0.026), TOPO-IIA (p=0.021) and TOPO-IIB (p=0.019) was correlated with shortened median overall survival (OS) in LS-SCLC patients. In patients with ES-SCLC, only high TOPO-IIB expression was associated with decreased OS (p=0.035). The favorable genotype (low expression of ERCC1, PKM2, TOPO-IIA and TOPO-IIB) was correlated with significantly improved PFS in both LS-SCLC (p<0.001) and ES-SCLC (p=0.007) patients as well as with improved OS in the LS-SCLC (p=0.007) and ES-SCLC (p=0.011) group. Unfavorable genotype was independent predictor of poor PFS (HR: 3.18; p=0.002) and OS (HR: 4.35; p=0.001) in LS-SCLC as well as for both PFS (HR: 3.14; p=0.021) and OS (HR: 3.32; p=0.019) in ES-SCLC. Conclusions: Single gene’s expression analysis as well as the integrated analysis of ERCC1, PKM2, TOPO-IIA and TOPO-IIB may predict treatment outcome in patients with SCLC. The results of our study, if validated prospectively, may help in selecting patients for personalized therapeutic strategies.

Phase II study to evaluate efficacy and safety of irinotecan, capecitabine, and bevacizumab in metastatic colorectal cancer (mCRC) patients.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 501-501 ◽  
Author(s):  
Pilar Garcia Alfonso ◽  
Manuel Chaves-Conde ◽  
Andres Munoz ◽  
Antonia Salud ◽  
Carlos Garcia-Giron ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Efficacy And Safety ◽  
Open Label ◽  
Ecog Performance Status ◽  
Combination Methods ◽  
Kras Status

501 Background: XELIRI regimen biweekly (combination of capecitabine and irinotecan) is an active and well tolerated treatment for mCRC. Bevacizumab provides significant clinical benefits in previously treated patients with mCRC. On this basis, the aim of this study is to evaluate the efficacy and safety of this combination. Methods: Multicentric, prospective, open-label phase II trial. Treatment scheme: irinotecan (iri) (175mg/m2 d1 q2w) + capecitabine (xel)(1,000mg/m2bid d 2-8) + bevacizumab (bev) (5mg/kg, d1 q2w). Results: 77 patients (p) were evaluated (66.2%, male) with a median age of 65.1 years (41.1-81.1). ECOG performance status was ≤1 in 96.1%. Primary tumor locations were: colon (53.2%), rectum (31.2%), and rectum/colon (15.6%). 27 p (35.1%) received adjuvant chemotherapy. Metastases were detected in liver (62.3%) and lung (54.5%). Mean time in treatment was: 7.1±4.9 months and median of cycles administered was 12(1-43). Median relative dose intensity was 89% for xel and bev and 85% for iri. Best response confirmed were: complete response (5.2%), partial response (32.5%), stable disease (46.8%). After a median of follow-up of 23.3 (0.4-39.6) months, median overall survival (OS) and progression free survival (PFS) was 24.8 and 11.8 months respectively. Analysis on Kras status was done in 71 p. There were no significant differences in OS or in PFS between WT and MUT p. 17 p (22.1%) underwent salvage surgery, 12 of whom had an R0 resection. The most frequent G3-4 toxicities were: diarrhea (18.2%), asthenia (16.9%), pulmonary embolism (13%; in eight of 10 p were asymptomatic), neutropenia (10.4%), febrile neutropenia (6.5%) and HFS (5.2%). Three treatment related deaths were reported (2 cases of multi-organ failure, and 1 case of intestinal perforation). Conclusions: Bevacizumab combined with biweekly XELIRI is an active first-line regimen for mCRC treatment with a feasible and manageable safety profile. Bevacizumab treatment efficacy was independent on Kras status. Clinical trial information: NCT00875771. [Table: see text]

First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9000-9000
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Expression Level ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

scholarly journals Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Free Survival

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

scholarly journals A Review of Docetaxel: Its Use in the Treatment of Gastric Cancer

2010 ◽  
Vol 2 ◽  
pp. CMT.S5191
Author(s):  
Alessandro Inno ◽  
Michele Basso ◽  
Alessandra Cassano ◽  
Carlo Barone
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Phase Iii ◽  
Poor Performance Status ◽  
Phase Ii Studies ◽  
Combination Regimens

Docetaxel, a member of the taxane family, promotes cell death by binding β-tubulin and has demonstrated activity against several human malignancies, both as a single agent and in combination therapy. It has been approved in Europe and the US as front-line treatment for advanced gastric cancer in combination with cisplatin and fluorouracil (DCF regimen). This approval was based on the results of a pivotal study (V325) which demonstrated that the addition of docetaxel to the reference regimen of cisplatin and fluorouracil improves overall survival and progression-free survival with a better quality of life despite increased toxicity (mainly haematological). Modifications of DCF regimen have been successfully investigated as a means of making the treatment more tolerable and suitable also for elderly patients or patients with poor performance status. Emerging data from several phase II studies suggest that other docetaxel-based combination regimens with anthracyclines or irinotecan have interesting activity with acceptable toxicity profiles, but the true efficacy of these regimens needs to be assessed in large randomized phase III studies. Thus, the best docetaxel-containing regimen has yet to be identified. Docetaxel also represents a good candidate for combination with novel molecular target agents. In light of the high response rates observed in phase II-III studies, a docetaxel-based chemotherapy regimen might also be considered a treatment option as perioperative or adjuvant therapy in potentially curable gastric cancer and further studies with or without biological agents are eagerly awaited in this setting.

scholarly journals Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation

2020 ◽  
Vol 38 (13) ◽  
pp. 1378-1388 ◽  
Author(s):  
Eileen M. O’Reilly ◽  
Jonathan W. Lee ◽  
Mark Zalupski ◽  
Marinela Capanu ◽  
Jennifer Park ◽  
...  
Keyword(s):  
Phase Ii ◽  
Group Performance ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
High Response Rate ◽  
Open Label ◽  
Free Survival ◽  
Palb2 Mutation

PURPOSE Five percent to 9% of pancreatic ductal adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (g BRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib treatment demonstrated a high response rate (RR), disease control rate (DCR), and overall survival (OS) in this population. We designed an open-label, randomized, multicenter, two-arm phase II trial to investigate cisplatin and gemcitabine with or without veliparib in g BRCA/PALB2+ PDAC. PATIENTS AND METHODS Eligible patients had untreated g BRCA/PALB2+ PDAC with measurable stage III to IV disease and Eastern Cooperative Oncology Group performance status of 0 to 1. Treatment for patients in arm A consisted of cisplatin 25 mg/m2 and gemcitabine 600 mg/m2 intravenously on days 3 and 10; treatment for patients in arm B was the same as that for patients in arm A, and arm A also received veliparib 80 mg orally twice per day on days 1 to 12 cycled every 3 weeks. The primary end point was RRs of arm A and arm B evaluated separately using a Simon two-stage design. Secondary end points were progression-free survival, DCR, OS, safety, and correlative analyses. RESULTS Fifty patients were evaluated by modified intention-to-treat analysis. The RR for arm A was 74.1% and 65.2% for arm B ( P = .55); both arms exceeded the prespecified activity threshold. DCR was 100% for arm A and 78.3% for arm B ( P = .02). Median progression-free survival was 10.1 months for arm A (95% CI, 6.7 to 11.5 months) and 9.7 months for arm B (95% CI, 4.2 to 13.6 months; P = .73). Median OS for arm A was 15.5 months (95% CI, 12.2 to 24.3 months) and 16.4 months for arm B (95% CI, 11.7 to 23.4 months; P = .6). Two-year OS rate for the entire cohort was 30.6% (95% CI, 17.8% to 44.4%), and 3-year OS rate was 17.8% (95% CI, 8.1% to 30.7%). Grade 3 to 4 hematologic toxicities for arm A versus arm B were 13 (48%) versus seven (30%) for neutropenia, 15 (55%) versus two (9%) for thrombocytopenia, and 14 (52%) versus eight (35%) for anemia. CONCLUSION Cisplatin and gemcitabine is an effective regimen in advanced g BRCA/PALB2+ PDAC. Concurrent veliparib did not improve RR. These data establish cisplatin and gemcitabine as a standard approach in g BRCA/ PALB2+ PDAC.

scholarly journals Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Free Survival

Abstract Background We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18). Results The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7–85.2; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2–86.4; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups. Conclusions This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

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