Chemoradiation with FOLFOX plus cetuximab in locally advanced cardia or esophageal cancer: Final results of a GERCOR phase II trial (ERaFOX).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 8-8 ◽  
Author(s):  
G. Lledo ◽  
P. Michel ◽  
L. Dahan ◽  
L. Mineur ◽  
M. Galais ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Induction Therapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Caloric Intake ◽  
Stage Iv ◽  
Stage Design ◽  
Platinum Based Chemotherapy ◽  
Stage Iv Disease ◽  
Grade 3

8 Background: Chemoradiotherapy (CRT) for locally advanced cardia and esophageal cancer is based on 5-FU combined with cisplatin, which could be favorably replaced by oxaliplatin (Ox). Cetuximab (C) has demonstrated synergism with both radiotherapy (RT) and platinum-based chemotherapy. ERaFOX trial was evaluating the safety and efficacy of the addition of C to CRT with FOLFOX. Methods: Main inclusion criteria were: stage III squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction; WHO PS 0-1; age 18-80 years; weight loss <15% in the last 6 months. Patients (pts) received 2 cycles of FOLFOX induction therapy (Ox 85 mg/m2/d1, folinic acid 400 mg/m2/d1, 5-FU 2,400 mg/m2/d1-2, q2w) plus C (first infusion 400 mg/m2 then 250 mg/m2, q1w), then RT 50.4 Gy (1.8Gy/d x 28 fractions) with FOLFOX plus C (same doses, except 5-FU 1,800mg/m2/d1-2). Tumor evaluation was performed at the end of CRT (RECIST and endoscopic ultrasonography). The primary endpoint was overall response rate (ORR), with a 50% threshold for efficacy (Simon Minimax two-stage design). Results: From Nov 2007 to Feb 2010, 80 pts were enrolled in 12 centers. The characteristics of the 79 eligible pts were (1 ineligible pt for stage IV disease): male/female 60/19, median age 63 (23-79), PS 0/1/ND 47/31/1, squamous/adenocarcinoma/undifferentiated 53/25/1; esophagus/cardia 74/5; median daily caloric intake 1,720 Kcal (550-3160). 74 pts were treated by CRT (5 pts experienced anaphylaxis during the first cetuximab infusion). ORR (ITT) was achieved in 61 pts (77.2%), 6 pts (7.6%) had stable disease, and 9 pts (11.4%) had disease progression (3 pts were not evaluable). Grade 3-4 toxicities induction therapy/CRT were (%): neutropenia: 7.6/28.4; febrile neutropenia: 0.0/2.7; vomiting: 1.3/4.0; mucositis: 1.3/5.4; diarrhea: 3.8/2.7; dysphagia-esophagitis: 1.3/13.5; rash: 7.6/10.8; allergy 8.9/0.0. One toxic death (1.3%) occurred after CRT related to esophagitis with GI bleeding. Conclusions: Threshold for efficacy was reached with an ORR of 77.2%. Chemoradiotherapy with FOLFOX plus cetuximab is active and has an acceptable toxicity profile in patients with locally advanced cardia or esophageal cancer. No significant financial relationships to disclose.

Cetuximab in combination with chemoradiotherapy prior to surgery in patients with resectable, locally advanced esophageal carcinoma: A prospective, multicenter phase lb-ll trial of the Swiss Group for Clinical Cancer Research (SAKK 75/06)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4570-4570
Author(s):  
T. Ruhstaller ◽  
M. Pless ◽  
J. C. Schuller ◽  
H. Kranzbühler ◽  
R. von Moos ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Phase Ii ◽  
Phase 1 ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiation ◽  
Thoracic Esophagus ◽  
Clinical Cancer Research ◽  
Intention To Treat ◽  
Grade 3

4570 Background: Cetuximab significantly enhances efficacy of radiotherapy and chemotherapy in head and neck cancer. We investigated the safety and feasibility of adding cetuximab to neoadjuvant chemoradiation of locally advanced esophageal cancer. Methods: Pts with resectable, locally advanced squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the thoracic esophagus or gastroesophageal junction (staged by EUS, CT and PET scan) were treated with 2 cycles of induction chemotherapy (docetaxel 75mg/m2, cisplatin 75mg/m2 q3w and weekly cetuximab 250mg/m2), followed by concomitant chemo- immuno-radiation therapy (CIRT: docetaxel 20mg/m2, cisplatin 25mg/m2 and cetuximab 250mg/m2 weekly five times concomitant with 45 Gy radiotherapy in 25 fractions); followed by surgery 4–8 weeks later. The phase I part consisted of 2 cohorts of 7 patients each, without and with docetaxel during CIRT, respectively. Interpatient dose-escalation (adding docetaxel during CIRT) was possible if < 2 out of 7 pts of the 1st cohort experienced limiting toxicity. Having finished the phase 1 part, 13 additional patients were treated with docetaxel-containing CIRT in a phase II part. Pathological response was evaluated according to the Mandard classification. Results: 27 pts from 12 institutions were included. As of today, results from 20 pts are available (cohort 1: 7, cohort 2: 7, phase ll : 6). Median age was 64yrs (range 47–71). 11 AC; 9 SCC. 19 pts (95%) completed CIRT (1 pt stopped treatment during induction therapy due to sepsis). 17 pts underwent resection (no surgery: 1pt for PD, 1pt for cardiac reasons). Grade 3 toxicities during CIRT included anorexia 15%, dysphagia/esophagitis 15%, fatigue 10%, nausea 10%, pruritus 5%, dehydration 5%, nail changes 5% and rash 5% .1 pt suffered from pulmonary embolism. 13 pts (65%, intention-to-treat) showed a complete or near complete pathological remission (cohort 1: 5, cohort 2: 4, phase II: 4). Conclusions: Adding cetuximab to preoperative chemoradiation for esophageal cancer is safe and feasible in a community-based multicenter setting. Antineoplastic activity is encouraging with 65% pathological responders. [Table: see text]

Adjuvant sunitinib following chemoradiotherapy (CRT) and surgery for esophageal cancer: A phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15550-e15550
Author(s):  
A. M. Horgan ◽  
G. Darling ◽  
R. Wong ◽  
A. Visbal ◽  
M. Guindi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Systemic Disease ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Thoracic Esophagus ◽  
Curative Intent ◽  
Post Surgery ◽  
Grade 3

e15550 Background: Locally advanced esophageal cancer (LAEC) has a 5-year survival of < 30 %. Most patients (pts) fail after curative intent tri-modality treatment with distant metastatic disease. This phase II trial aims to determine if adjuvant targeted therapy, after neoadjuvant CRT plus surgery for resectable LAEC, may impact on systemic disease without significant toxicity. Methods: Pts with LAEC of the thoracic esophagus or gastroesophageal junction, ECOG PS 0,1 and surgical candidates treated with: preoperative Irinotecan (65mg/m2 initially, ammended to 50mg/m2) + Cisplatin (30mg/m2) on weeks 1,2,4,5,7,8 + concurrent conformal radiotherapy (50Gy/25 fractions) on weeks 4–8. Esophagectomy during weeks 15–18. Sunitinib 37.5mg daily (escalating to 50mg daily if tolerated) commenced 4–12 weeks post surgery, for 1 year. Primary endpoint is feasibility and efficacy of adjuvant sunitinib. Planned sample size 36pts. Results: 30pts enrolled from 11/06 to 12/08. Median age 64 yr (43–71), male: 22, adenocarcinoma: squamous 22:6; 10 pts stage IIA, 5 IIB and 13 III. 2 pts excluded with positive PET scan. 28 pts completed CRT - 18 pts (64%) received ≥80% of planned chemotherapy dose, 23 pts (82%) received full radiation dose. Grade 3/4 toxicity included: neutropenia (17/28), diarrhea (7/28), dehydration (4/28), febrile neutropenia (FN) (3/28) and nausea (2/28). 2 deaths on chemotherapy (1 bacterial meningitis, 1 FN) leading to irinotecan dose- reduction. Dysphagia improved in 14/23 pts during CRT. 18 pts have undergone esophagectomy. Complete pathological response in 4 (22%), downstaging in 3 (17%), stable disease in 11 (61%). 2 pts unresectable (metastases at laparotomy). 1 post-operative death due to pulmonary embolus. 9 pts have commenced sunitinib, 6 maintained at starting dose of 37.5mg; 2 dose reductions; 1 discontinued with poor wound healing. Grade 3 toxicity included: leukopenia (2/9), hand-foot reaction (1/9) and depression (1/9). Conclusions: In LAEC, induction Irinotecan/Cisplatin and radiotherapy followed by esophagectomy is associated with a significant but manageable toxicity profile. Early initiation of sunitinib is feasible and well-tolerated. Updated results to be presented. No significant financial relationships to disclose.

FORT-1: Phase II/III study of rogaratinib versus chemotherapy (CT) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) selected based on FGFR1/3 mRNA expression.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 489-489 ◽  
Author(s):  
David I. Quinn ◽  
Daniel Peter Petrylak ◽  
Joaquim Bellmunt ◽  
Andrea Necchi ◽  
Howard Gurney ◽  
...  
Keyword(s):  
Phase Ii ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Open Label ◽  
Activating Mutations ◽  
Stage Iv Disease ◽  
Dna Alterations ◽  
Grade 3 ◽  
Muscle Invasive

489 Background: Aberrant activation of fibroblast growth receptor (FGFR) signaling plays a role in UC. Rogaratinib, a pan-FGFR1-4 inhibitor, has promising efficacy and safety in pts with advanced muscle-invasive UC, selected based on FGFR1-3 mRNA overexpression and/or FGFR3-activating mutations/translocations. This Phase II/III, randomized, open-label study evaluated the efficacy of rogaratinib vs CT in pts with FGFR-positive advanced or metastatic UC who received prior platinum CT. We present an ORR analysis for rogaratinib vs CT. Methods: FGFR1/3 mRNA was tested by in situ hybridization of archival tissue. Pts were randomized 1:1 to 800 mg rogaratinib p.o. BID continuously or CT Q3W (i.v., docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2), and stratified by PIK3CA/ RAS-activating mutations, prior immunotherapy, and modified 4-factor Bellmunt risk score. Results: 87 pts were assigned to rogaratinib and 88 to CT. Overall, 82.9% were male, median age was 69.0 yrs (range: 36-89), 96.6% had stage IV disease, and 2.3% were stage IIIB. PIK3CA/ RAS-activating mutations were present in 11.4% of pts. ORRs of 19.5% and 19.3% (1-sided p=0.56) and disease control rates of 49.4% and 55.7% (p=0.84) were observed for rogaratinib and CT, respectively; median progression-free survival was 2.7 months (95% CI 1.6, 4.2) and 2.9 months (95% CI 2.6, 4.2). Grade 3-4 treatment-emergent adverse events occurred in 40/86 pts (47%) treated with rogaratinib and 46/82 pts (56%) with CT, most commonly anemia (3% vs 15%), neutropenia (1% vs 17%), asthenia (9% vs 1%), lipase increase (8% vs 2%), fatigue (2% vs 6%), and urinary tract infection (2% vs 6%). Exploratory analysis of pts with FGFR3 DNA alterations (4 spot mutations and fusions) showed ORRs of 52.4% with rogaratinib and 26.7% with CT. Conclusions: In pts with FGFR1/3 tumor mRNA-positive UC, rogaratinib had efficacy comparable with standard CT and an acceptable safety profile. Subgroup analysis suggests rogaratinib may be more active in pts with an FGFR3 DNA alteration. Sensitivity analysis of biomarker subgroups is ongoing. Clinical trial information: NCT03410693.

Cetuximab (C-mab) and chemo-radiation (CT-RT) for loco-regional advanced squamous cell carcinoma of the head and neck (HNC): A phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6043-6043 ◽  
Author(s):  
M. C. Merlano ◽  
G. Numico ◽  
E. G. Russi ◽  
M. Benasso ◽  
I. Colantonio ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Stage Iv ◽  
Skin Toxicity ◽  
Activity Data ◽  
Stage Design ◽  
Colon Diverticulitis ◽  
Oral Cavity Tumor ◽  
Grade 3 ◽  
Fatal Myocardial Infarction

6043 Background: C-mab is a monoclonal antibody targeting EGFR. C-mab combined with radiotherapy (RT) improved loco- regional control and overall survival over RT alone in HNC pts (Bonner 2006). Prior data of C-mab and CT-RT (Pfister 2006) were encouraging but the trial was stopped due to an excess of severe toxicities, suggesting the need for a less toxic scheduling. For these reasons we evaluate the safety and activity of C-mab combined with alternating CT-RT in HNC pts. Methods: The primary end-point is C.R. rate. The optimal two stage design was used: the calculated sample size is 45 pts. Eligible pts have locally advanced, measurable, untreated, stage III/IV HNC (excluding nasopharynx). Chemotherapy (CT) consists of Cis-PT 20 mg/m2/day and bolus 5Fu 200 mg/m2/day from day 1 to 5, repeated on days 22 and 43. RT, 2 Gy/day, 5 days a week, is given in the pauses between the chemotherapy courses and after the last CT week, up to a total dose of 70 Gy. Results: From 10/2005 to 12/2006 24 pts were enrolled: median age 59 (49–75); median ECOG P.S. 0 (0–1); Stage IV 73%; N1–3 86%; EGFR >80% cells: 55%; EGFR 3+: 91%; most pts had hypopharynx cancer, only 1 had oral cavity tumor. Toxicity is evaluable on 20 pts (4 ongoing). Grade 3–4 toxicities included febrile neutropenia (20%), diarrhea (20%), hypomagnesaemia (10%), mucositis (60%). Unexpected skin toxicity, starting as desquamating moist dermatitis and confined at the irradiated field, occurred in 18/20 pts, usually during the second part of the treatment. Acute colon diverticulitis with perforation (1 pt), gastric perforation (1 pt), fatal myocardial infarction (1 pt) and arterial thrombosis (1 pt) also occurred. Responses, evaluated 3 months after the treatment, are available for the first 16 pts. Objective responses were observed in all them (11 CR + 5 PR). Two PRs were then rendered disease free with salvage surgery. At a maximum follow-up of 15 months, 16/20 pts are alive and 16/20 progression free. Conclusions: This trial showed a skin toxicity not previously reported in other experiences of C-mab combined with RT or CT-RT. Preliminary activity data seems to confirm the Pfister experience. No significant financial relationships to disclose.

281 JAVELIN Medley VEGF: phase 2 study of avelumab + axitinib in patients with previously treated non-small cell lung cancer (NSCLC) or treatment naive, cisplatin-ineligible urothelial cancer (UC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A307-A307
Author(s):  
Gabriella Galffy ◽  
Iwona Lugowska ◽  
Elena Poddubskaya ◽  
Byoung Chul Cho ◽  
Myung-Ju Ahn ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Maintenance Treatment ◽  
Locally Advanced ◽  
Small Cell Lung ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Open Label Phase ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Grade 3

BackgroundAvelumab, a human anti–PD-L1 monoclonal antibody, has shown a manageable safety profile and antitumor activity in multiple tumor types, including platinum-resistant metastatic or recurrent NSCLC,1 and is approved for patients with locally advanced or metastatic UC who have progressed after ≥1 previous line of platinum-based chemotherapy2 3 and as maintenance treatment for those who have not progressed with platinum-based chemotherapy.4 JAVELIN Medley VEGF (NCT03472560) evaluated the efficacy and safety of avelumab + axitinib, a potent inhibitor of VEGFR 1, 2, and 3, in patients with advanced or metastatic NSCLC or UC.MethodsEligible patients with NSCLC had received ≥1 prior platinum-containing therapy and ≤2 prior lines of systemic therapy for locally advanced or metastatic disease; patients with UC were treatment naive in the locally advanced or metastatic setting and ineligible for cisplatin-containing chemotherapy. Patients were immune checkpoint inhibitor naïve and received avelumab 800 mg intravenously every 2 weeks + axitinib 5 mg orally twice daily. The primary endpoint was confirmed objective response (OR) per investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS) and safety. PD-L1 expression was assessed in baseline tumor samples (Ventana SP263 assay). Data have not undergone standard quality checks and are subject to change due to COVID-19–related healthcare burden.ResultsA total of 41 patients with NSCLC and 20 with UC received avelumab + axitinib. The confirmed OR rate was 31.7% (95% CI, 18.1–48.1) in the NSCLC cohort and 10% (95% CI, 1.2–31.7) in the UC cohort (all partial responses); 16 patients (39.0%) and 5 (25.0%) had stable disease, respectively. Responses were observed regardless of PD-L1 expression status. Median PFS was 5.5 months (95% CI, 2.5–7.0) in the NSCLC cohort and 2.3 months (95% CI, 1.8–5.6) in the UC cohort. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 24 patients (58.5%) in the NSCLC cohort; the most common was hypertension (n=7 [17.1%]). Grade ≥3 TRAEs occurred in 9 patients (45.0%) in the UC cohort; the most common were amylase increased, asthenia, decreased appetite, and palmar-plantar erythrodysesthesia syndrome (n=2 [10%] each). One patient in each cohort experienced a TRAE that led to death (gastric perforation and urinary bladder hemorrhage).ConclusionsAvelumab + axitinib showed antitumor activity and a manageable safety profile in patients with advanced or metastatic NSCLC or UC consistent with findings from studies of each drug alone and in combination.Trial RegistrationNCT03472560Ethics ApprovalThe study was approved by each site’s independent ethics committee.ConsentN/AReferencesGulley JL, Rajan A, Spigel DR, et al. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol 2017;18:599–610.Patel MR, Ellerton J, Infante JR, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol 2018;19:51–64.Bavencio(avelumab) injection. [package insert] Darmstadt, Germany: Merck KGaA; 2019.US Food and Drug Administration. FDA approves avelumab for urothelial carcinoma maintenance treatment. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avelumab-urothelial-carcinoma-maintenance-treatment. Accessed August 19, 2020.

Phase I Trial of Escalating-Dose Irinotecan Given Weekly With Cisplatin and Concurrent Radiotherapy in Locally Advanced Esophageal Cancer

2003 ◽  
Vol 21 (15) ◽  
pp. 2926-2932 ◽  
Author(s):  
David H. Ilson ◽  
Manjit Bains ◽  
David P. Kelsen ◽  
Eileen O’Reilly ◽  
Martin Karpeh ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Phase I ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Phase I Trial ◽  
Locally Advanced ◽  
Phase Iii ◽  
Concurrent Radiotherapy ◽  
Minimal Toxicity ◽  
Grade 3

Purpose: To identify the maximum-tolerated dose and dose-limiting toxicity (DLT) of weekly irinotecan combined with cisplatin and radiation in esophageal cancer. Patients and Methods: Nineteen patients with clinical stage II to III esophageal squamous cell or adenocarcinoma were treated on this phase I trial. Induction chemotherapy with weekly cisplatin 30 mg/m2 and irinotecan 65 mg/m2 was administered for four treatments during weeks 1 to 5. Radiotherapy was delivered weeks 8 to 13 in 1.8-Gy daily fractions to a dose of 50.4 Gy. Cisplatin 30 mg/m2 and escalating-dose irinotecan (40, 50, 65, and 80 mg/m2) were administered on days 1, 8, 22, and 29 of radiotherapy. DLT was defined as a 2-week delay in radiotherapy for grade 3 to 4 toxicity. Results: Minimal toxicity was observed during chemoradiotherapy, with no grade 3 or 4 esophagitis, diarrhea, or stomatitis. DLT caused by myelosuppression was seen in two of six patients treated at the 80-mg/m2 dose level, thus irinotecan 65 mg/m2 was defined as the recommended phase II dose. Dysphagia improved or resolved after induction chemotherapy in 13 (81%) of 16 patients who reported dysphagia before therapy. Only one patient (5%) required a feeding tube. Six complete responses (32%) were observed, including four pathologic complete responses in 15 patients selected to undergo surgery (27%). Conclusion: Cisplatin, irinotecan, and concurrent radiotherapy can be administered on a convenient schedule with relatively minimal toxicity and an acceptable rate of complete response in esophageal cancer. Further phase II evaluation of this regimen is ongoing. A phase III comparison to fluorouracil or taxane-containing chemoradiotherapy should be considered.

Major Pathologic Response after Induction Therapy Has a Long-Term Impact on Survival and Tumor Recurrence in Stage IIIA/B Locally Advanced NSCLC

2019 ◽  
Vol 68 (07) ◽  
pp. 639-645
Author(s):  
Waldemar Schreiner ◽  
Wojciech Dudek ◽  
Ralf Joachim Rieker ◽  
Sebastian Lettmaier ◽  
Rainer Fietkau ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Lung Resection ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Pathologic Response ◽  
Perioperative Morbidity ◽  
Platinum Based Chemotherapy ◽  
Impact On Survival ◽  
Long Term Impact

Abstract Background Major pathologic response (MPR) determines favorable outcome in locally advanced non-small cell lung cancer after induction therapy (IT) followed by lung resection. The aim of this retrospective study was to identify the prognostic relevance of MPR in long-term interval. Methods In 55 patients, the survival rate according to MPR and non-MPR was estimated by Kaplan–Meier method and compared using log-rank, Breslow, and Tarone–Ware tests. Results The IT included chemoradiation with 50.4 Gy (range: 45–56.4 Gy) combined with platinum-based chemotherapy in 52 patients (94.5%) and platinum-based chemotherapy in 3 patients (5.5%). Perioperative morbidity and 30-day mortality were 36 and 3.6%, respectively. The estimated 5-year postoperative and progressive-free survivals were statistically significantly improved in MPR versus non-MPR with 53.5 versus 18% and 49.4 versus 18.5%, respectively. According to the log-rank, Breslow, and Tarone–Ware tests, the MPR demonstrates prognostic significance in early, long-term, and whole postoperative interval. Conclusion MPR is associated with a robust correlation to long-term postoperative and recurrence-free survival improvement, and can potentially simplify the multidisciplinary debate and allow further stratification of adjuvant treatment in multimodality therapy.

Treatment of advanced carcinoma of the vulva with chemoradiotherapy — can exenterative surgery be avoided?

1994 ◽  
Vol 4 (3) ◽  
pp. 150-155 ◽  
Author(s):  
D. J. Sebag-Montefiore ◽  
C. Mclean ◽  
S. J. Arnott ◽  
P. Blake ◽  
P. Van Dam ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Stage Iv ◽  
Complete Response ◽  
Figo Stage ◽  
Who Grade ◽  
Low Toxicity ◽  
Venous Infusion ◽  
Grade 3 ◽  
Extent Of Disease ◽  
Disease Free

Thirty-seven patients with advanced FIGO stage (17 stage III, 20 stage IV) carcinoma of the vulva whose extent of disease would have required extenterative surgery were treated with chemoradiotherapy (CRT). Radiotherapy was given as a split course (2500 cGy mid-plane dose in 10 daily fractions, repeated 1 month later) to the first seven patients. Subsequently radiotherapy was given as a continuous course (4500 cGy mid-plane dose in 20–25 daily fractions). Chemotherapy included mitomycin c as an intravenous bolus and 5 fluorouracil as a continuous intra-venous infusion over 4–5 days, with variations in timing and dose according to the type of radiotherapy course. Fifteen (47%) complete and 11 (34%) partial responses were seen at 3 months after completion of treatment. Of the 15 patients with complete response, 10 remained disease-free for a median of 24 months (range 6–36 months). The median sur-vival for complete and partial responding patients was 15 and 11 months, respectively (range 2–37 months). Acute toxicity included moist perineal desquamation, diarrhea and myelosupression. One death secondary to neutropaenic sepsis occurred in the split course group. WHO grade 3 radiation enteritis occurred in one patient (14%) in the split course and two patients (6%) in the continuous CRT groups. Using CRT, very high response rates have been obtained with relatively low toxicity. There is a useful role for CRT in the treatment of patients with locally advanced recurrent disease although its place in the management of extensive primary disease requires further evaluation.

Final Results of a Phase II Trial of Belinostat (PXD101) in Patients with Recurrent or Refractory Peripheral or Cutaneous T-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 920-920 ◽  
Author(s):  
Brad Pohlman ◽  
Ranjana Advani ◽  
Madeleine Duvic ◽  
Kenneth B. Hymes ◽  
Tanin Intragumtornchai ◽  
...  
Keyword(s):  
T Cell ◽  
Median Duration ◽  
Cell Lymphoma ◽  
Stage Iv ◽  
T Cell Lymphoma ◽  
Cutaneous Lesions ◽  
Stage Iv Disease ◽  
Duration Of Response ◽  
Post Infusion ◽  
Grade 3

Abstract Abstract 920 Background: Belinostat is a pan-HDAC inhibitor of the hydroxamate chemical class that is well-tolerated and has shown clinical activity. Methods: Open label, multicenter trial enrolling patients (pts) with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who failed ≥ 1 prior systemic therapy. Pts received 1000 mg/m2 IV belinostat over 30 min on days 1 to 5 of a 3-wk cycle. Primary endpoint was objective response (OR) assessed by IWG criteria for PTCL and by SWAT (cutaneous lesions) and IWG criteria (non-cutaneous lesions) for CTCL. Pruritus in pts with CTCL was assessed using a 10-point scale; relief defined as reduction of pruritus score of ≥ 3 points in pts with baseline score ≥ 3. ECGs were monitored and reviewed centrally (pre-/ post-infusion ECGs on all treatment days in cycle 1, and pre-/ post-infusion ECGs on day 1 of subsequent cycles) to evaluate potential cardiac toxicity. Results: The study enrolled a total of 53 treated pts, including 20 and 29 evaluable pts with a diagnosis of PTCL and CTCL, respectively. The 20 pts with PTCL [10 PTCL-unspecified (PTCL-U), 3 anaplastic large cell lymphoma (ALCL), 3 angioimmunoblastic TCL (AITL), 3 NK/T-cell lymphoma, and 1 subcutaneous panniculitis-like TCL (SPTCL)] had received a median of 3 prior systemic therapies (range 1 – 10), and 40 % of them had stage IV disease. 5/20 (25%) PTCL pts responded with 2 CR (both in patients with PTCL-U) and 3 PR (PTCL-U, AITL, ALCL). The 5 responding pts had a median duration of response of 159+ days (range 1 – 504+). Additionally, SD was observed in 5 pts (2 PTCL-U, 2 NK/T-cell, and 1 ALCL) with median duration of SD of 109+ days (range 80 -185+). The 29 pts with CTCL [15 mycosis fungoides (MF), 7 Sezary syndrome (SS), 5 non MF/SS, 2 unclassified] had received a median of 1 prior skin directed therapies (range 0 – 4) and 3 prior systemic therapies (range 1 – 9), and 55 % of them had stage IV disease. 4/29 (14%) CTCL pts responded with 2 CR (ALCL, MF) and 2 PR (MF, SS). The 4 responding pts had a median duration of response of 273 days (range 48 - 469+). Importantly, time to response was short with a median of 16 days (range 14-35). In addition, SD was observed in 17 pts (10 MF, 3 SS, 2 non MF/SS, 2 unclassified) with current duration of up to 127 days. Pruritus relief (score reduction ≥ 3) was seen in 7 of 14 pts with significant baseline pruritis. Median time to pruritus relief was also short, 16 days (range 7-45). Hematological toxicity was minimal without any grade 4 events (shift from baseline) and only one pt each experiencing grade 3 neutropenia and grade 3 thrombocytopenia, respectively. No grade 3 QTcF prolongation was detected in more than 700 ECGs. Four grade 3/4 drug-related AEs were reported: pruritis, rash/erythema, edema, and adynamic ileus. Conclusions: Belinostat monotherapy is safe, well tolerated, and efficacious in pts with recurrent/refractory T-cell lymphoma with durable remissions in both CTCL and PTCL. These results are the basis for a pivotal study with belinostat monotherapy in pts with PTCL. Disclosures: Advani: Seattle Genetics, Inc.: Research Funding. Duvic:Topotarget: research support for conduct of clinical trial. Fagerberg:TopoTarget A/S: Employment, Equity Ownership. Foss:Eisai : Speakers Bureau.

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