5-fluorouracil (5-FU) plus cisplatin (CDDP) induction chemotherapy followed by combined external bean radiation therapy (XRT) and mitomycin-C (MMC) and 5-FU chemotherapy in locally advanced anal canal cancer (ACC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14016-14016
Author(s):  
J. J. Rodriguez-Riao ◽  
D. Figueira ◽  
E. Zarraga ◽  
L. Lion ◽  
M. B. Fuentes ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Complete Response ◽  
Sphincter Preservation ◽  
Combined Modality Treatment ◽  
Anal Canal Cancer ◽  
Grade 3 ◽  
Ecog Ps

14016 Background: Definitive chemoradiation therapy is the standard of care for squamous or cloacogenic cell ACC. The chemotherapy regimen comprising 5-FU and MMC is the most commonly used among patients with ACC, nearly 70% of patients can get complete response (CR), with the benefit of sphincter preservation, but patients with a large tumors (T3/T4) or nodal metastases have a response of 50%. Methods: To improve outcome, we conducted a phase II, study of 5-FU and CDDP followed by combined XRT plus 5-FU and MMC. Eligibility included patients withT3/T4 ACC with limited locoregional nodal involvement (N0/N1). Treatment: 5-FU 1000 mg/m2/days 1 to 5 in continuous i.v. infusion plus CDDP 100 mg/m2 i.v. day 1 q21d was administered for 2 cycles (weeks 1 and 4) followed by XRT (4.5 Gy) during 6 weeks (weeks 7 to12) with concurrent 5-FU 1000 mg/m2/days 1 to 4 in continuous i.v. infusion plus MMC 10 mg/m2 i.v. day 1 (weeks 9 and 17). RECIST criteria were used to assess tumor response Results: 59 patients were entered on this study from 8/2000 to 2/2005. Median age: 57 yrs (37–83), 49 F/10 M, median ECOG PS 0 (0–1), T3/T4 44/15, N0/N1 20/39. 54 patients were evaluable for clinical response: Induction chemotherapy led to 13 (24%) CR, 38 (70%) partial responses (PR) and 2 (6%) stable disease. After combined modality treatment, there were a total of 36 (67%) CR, 13 (24%) PR, 5 (9%) SD. Median follow up was 21.6 months (5–52).The median time to progression is 20.5 months (3–52). Toxicity grade 3/4: Neutropenia 20% (10/54), thrombocytopenia 13% (7/54), radiodermatitis 13% (7/54), nausea/vomiting 7% (4/54). Our previous experience with concurrent treatment without induction (n=27) resulted in a CR 59%, PR 37%, and 4% progressive disease Conclusions: We concluded that induction chemotherapy followed by combined XRT and chemotherapy could be an option in treatment of locally advanced ACC. No significant financial relationships to disclose.

Updated results of a phase II trial integrating gefitinib (G) into concurrent chemoradiation (CRT) followed by G adjuvant therapy for locally advanced head and neck cancer (HNC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6028-6028 ◽  
Author(s):  
S. M. Ahmed ◽  
E. E. Cohen ◽  
D. J. Haraf ◽  
K. M. Stenson ◽  
E. Blair ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Locally Advanced ◽  
Stage Iv ◽  
Early Death ◽  
Complete Response ◽  
Poorly Differentiated ◽  
Patient Refusal ◽  
Grade 3 ◽  
Ecog Ps

6028 Background: This study was undertaken to evaluate the tolerability and efficacy of substituting G for paclitaxel into a well- described CRT regimen (Clin Cancer Res 9: 5936; JCO 21: 320) and continuing G as adjuvant therapy. Endpoints included complete response (CR) rate to CRT, progression-free (PFS), disease-specific (DSS) and overall survival (OS), and local & distant control rates. Methods: Previously untreated subjects with stage III, IVa, or IVb squamous cell, poorly differentiated carcinomas, or lymphoepithelioma were enrolled. Organ sparing surgery was allowed. Subjects received 2 cycles of carboplatin/paclitaxel induction followed by CRT with G (250 mg PO qd), 5- fluorouracil, hydroxyurea, and twice daily radiation on day 1–5 of five 14d cycles. G was continued for 2 years from the start of CRT. Results: From 2/03 to 10/04, 67 eligible subjects accrued including 51 males; median age 56; ECOG PS 0 in 47, 1 in 19, and 2 in 1; stage IV in 61 (91%). With median follow-up of 858 days, 9 have had progressive disease (PD, 3 distant, 5 local, 1 with both) and 15 have died (12 related to HNC). Estimated OS=83% at 2y, 73% at 3y; PFS=77% at 2y, 64% at 3y; and DSS=86% at 2y, 80% at 3y. In 56 evaluable subjects we observed 51 CR (91 %), 4 partial responses and 1 PD after CRT. Non-evaluable subjects underwent surgery prior to CRT (10), or died prior to evaluation (1). Grade 3/4 toxicity included mucositis (75%/10%), dermatitis (29%/3%), rash (4%/0%) and diarrhea (1%/0%). Sixty-two patients received maintenance gefitinib, with 60 reliably reporting doses (median days on gefitinib=667). Reasons for holding G included LFT abnormalities, patient refusal, diarrhea, rash, recurrence, hospitalization for acute illness, and early death. Conclusions: Adding G to concurrent CRT after induction therapy, and as adjuvant therapy is tolerable and feasible. Favorable survival and CR data suggest that this is a promising regimen for patients with locally advanced HNC. [Table: see text]

Feasibility study of capecitabine (cap) and cisplatin (cis) with radiation therapy (RT) in the management of patients with locally advanced unresectable squamous cell carcinoma of the head and neck (HNSCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16520-16520
Author(s):  
J. W. Allen ◽  
S. Vasireddy ◽  
J. Kaufman ◽  
J. M. Hughes ◽  
M. Sebelik ◽  
...  
Keyword(s):  
Medical Center ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Complete Response ◽  
Percutaneous Gastrostomy ◽  
Treatment Delays ◽  
Male Patients ◽  
Grade 3 ◽  
Dose Modifications

16520 Background: Concurrent chemoradiation has become the standard of care for locally advanced unresectable HNSCC. The most commonly used chemotherapy is cis and 5-fluorouracil (5-FU). We evaluated the feasibility of using cap and cis during RT in this population. Cap is an oral pro-drug of 5-FU that can be given daily with RT in order to enhance the activity of RT. Methods: Between Oct, 2003 and Sept, 2005, 12 male patients aged 46–83 were treated at the VA Medical Center. Patients received cis 100 mg/m2 on days 1 and 29 and cap 450 mg/m2 bid (2 hours prior to RT and 12 hours later) for 5 days of each week concurrent with RT to a total dose of 70 Gy in 35 fractions over 7 weeks. Primary endpoint of the study was toxicity. Results: All 12 patients were able to complete therapy. Treatment delays and/or dose modifications were needed in 7 patients. Treatment related toxicities included 6 patients with grade 3 mucositis and 5 patients with grade 3 dysphagia. Other grade 3 toxicities included 3 patients with dehydration and 1 patient each with leucopenia, constipation, nausea and vomiting, and odynophagia. Percutaneous gastrostomy (PEG) tubes were required in 5 patients. Complete response to chemoradiation was seen in 9 patients, 2 patients obtained partial response, and 1 patient progressed. Median progression free and overall survivals have not been reached with a median follow-up of 21 months. Conclusions: Cis and cap administered concurrently with RT has manageable toxicities and is active in patients with locally advanced unresectable HNSCC. No significant financial relationships to disclose.

Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 205-205
Author(s):  
Daisuke Takahari ◽  
Manabu Ohashi ◽  
Atsuo Takashima ◽  
Takuro Mizukami ◽  
Naoki Ishizuka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Complete Response ◽  
Free Survival ◽  
D2 Gastrectomy ◽  
Locally Advanced Gastric Cancer ◽  
Grade 3

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in < 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.

REGN2810: A fully human anti-PD-1 monoclonal antibody, for patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC)—Initial safety and efficacy from expansion cohorts (ECs) of phase I study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9503-9503 ◽  
Author(s):  
Kyriakos P. Papadopoulos ◽  
Taofeek Kunle Owonikoko ◽  
Melissa Lynne Johnson ◽  
Irene Brana ◽  
Marta Gil-Martin ◽  
...  
Keyword(s):  
Phase 1 ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Initial Response ◽  
Complete Response ◽  
Median Number ◽  
Whole Exome ◽  
Tumor Measurements ◽  
Prior Systemic Therapy ◽  
Grade 3

9503 Background: There is no established standard of care for unresectable locally advanced or metastatic CSCC. UV-induced DNA damage causes hypermutation in most CSCCs. Therefore, these tumors may be responsive to PD-1 checkpoint blockade. In the dose escalation portion of the phase 1 study of REGN2810, a durable (19 + months) radiologic complete response was observed in a patient (pt) with metastatic CSCC (ASCO 2015, #3024). Methods: ECs enrolled pts with distantly metastatic (EC 7) and locally advanced (EC 8) CSCC. All patients received 3 mg/kg REGN2810 by intravenous infusion over 30 minutes every 2 weeks for up to 48 weeks. Research biopsies were performed at baseline and Day 29 (and at progression, if possible). Tumor measurements were performed every 8 weeks according to RECIST 1.1 to determine overall response rate (ORR). Data cutoff date was 31 Jan 2017. Results: 26 pts were enrolled (10 in EC 7 and 16 in EC 8): median age, 72.5 y (range, 56-88y); median PS 1 (range, 0 – 1); 21M:5F; median number of prior systemic therapy regimens, 1 (range, 0 – 2). Median exposure to REGN2810 was 7 doses (range, 1-22). The most common treatment-related adverse event of any grade was fatigue (19.2%). Each of the following ≥ Grade 3 related AEs occurred once: AST elevation, ALT elevation, arthralgia, and rash. ORR (PR + CR, including unconfirmed) and disease control rate (ORR+SD) were 52% (12/23; 4uPR, 5 PR, 2CR, 1 uCR) and 70% (16/23, including 4SD), respectively. Three patients are not yet evaluable. Median PFS and OS have not been reached, and only one patient has experienced PD during REGN2810 treatment after initial response. Correlative studies are in process, including PD-L1 status and whole exome tumor DNA sequencing. Conclusions: REGN2810 is well tolerated and produces antitumor activity in patients with advanced CSCC. A pivotal trial of REGN2810 for patients with advanced CSCC is enrolling patients (NCT02760498). Clinical trial information: NCT02383212.

Cemiplimab (REGN2810): A fully human anti-PD-1 monoclonal antibody for patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC)—Initial safety and efficacy from expansion cohorts (ECs) of phase I study.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 195-195 ◽  
Author(s):  
Kyriakos P Papadopoulos ◽  
Taofeek Kunle Owonikoko ◽  
Melissa Johnson ◽  
Irene Brana ◽  
Marta Gil Martin ◽  
...  
Keyword(s):  
Phase 1 ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Initial Response ◽  
Complete Response ◽  
Median Number ◽  
Whole Exome ◽  
Tumor Measurements ◽  
Prior Systemic Therapy ◽  
Grade 3

195 Background: There is no established standard of care for unresectable locally advanced or metastatic CSCC. UV-induced DNA damage causes hypermutation in most CSCCs. Therefore, these tumors may be responsive to PD-1 checkpoint blockade. In the dose escalation portion of the phase 1 study of cemiplimab (REGN2810), a durable (19 + months) radiologic complete response was observed in a patient (pt) with metastatic CSCC (ASCO 2015, #3024). Methods: ECs enrolled pts with distantly metastatic (EC 7) and locally advanced (EC 8) CSCC. All patients received cemiplimab 3 mg/kg by intravenous infusion over 30 minutes every 2 weeks for up to 48 weeks. Research biopsies were performed at baseline and Day 29 (and at progression, if possible). Tumor measurements were performed every 8 weeks according to RECIST 1.1 to determine overall response rate (ORR). Data cutoff date was 31 Jan 2017. Results: 26 pts were enrolled (10 in EC 7 and 16 in EC 8): median age, 72.5 y (range, 56–88y); median PS 1 (range, 0–1); 21M:5F; median number of prior systemic therapy regimens, 1 (range, 0–2). Median exposure to cemiplimab was 7 doses (range, 1–22). The most common treatment-related adverse event of any grade was fatigue (19.2%). Each of the following ≥ Grade 3 related AEs occurred once: AST elevation, ALT elevation, arthralgia, and rash. ORR (PR + CR, including unconfirmed) and disease control rate (ORR+SD) were 52% (12/23; 4uPR, 5 PR, 2CR, 1 uCR) and 70% (16/23, including 4SD), respectively. Three patients are not yet evaluable. Median PFS and OS have not been reached, and only one patient has experienced PD during cemiplimab treatment after initial response. Correlative studies are in process, including PD-L1 status and whole exome tumor DNA sequencing. Conclusions: Cemiplimab is well tolerated and produces antitumor activity in patients with advanced CSCC. A pivotal trial of cemiplimab for patients with advanced CSCC is enrolling patients. Clinical trial information: NCT02383212.

scholarly journals Induction Chemotherapy Followed by Concurrent Chemo-Radiotherapy for Locally Advanced Gastro-Esophageal and Gastric Carcinoma

2021 ◽  
pp. 35-44
Author(s):  
Nora Shaband ◽  
Niveen Abo-Touk ◽  
Mohamed Elawadi ◽  
Saleh Ta-Ema
Keyword(s):  
Induction Chemotherapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Esophageal Stenosis ◽  
University Hospital ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Gastroesophageal Adenocarcinoma

Aims: To assess the safety and efficacy of chemo-radiotherapy before radical surgery in locally advanced gastric and gastroesophageal adenocarcinoma. Study Design: This was a prospective phase Ⅱ single arm study. Place and Duration of Study: Department of Clinical Oncology and Nuclear Medicine, Mansoura University Hospital, Mansoura, Egypt, between May 2017 and June 2019. Methodology: Patients with pathologically proven gastric or gastroesophageal junction adenocarcinoma are included. They received one cycle of induction chemotherapy paclitaxel-carboplatin, [paclitaxel dose of 175 mg/m2, carboplatin dose of (AUC: 5)], followed by CCRT [RT 45 Gy over 25 fractions over 5 weeks concurrent with weekly paclitaxel at a dose of 50 mg/m2, carboplatin at a dose of (AUC: 2)], followed by surgery and 2 cycles of paclitaxel-carboplatin for responders. Results: The study included 24 patients. Most of the patients were diagnosed at stage III (83.3%). There were no major side effects of the induction chemotherapy cycle. There were no reported grade 3 or 4 toxicities for the CCRT. Only two patients suffered from late radiation toxicities (distal esophageal stenosis). Pathological complete response was achieved in seven patients (31.8%). Twenty-two patients had surgical resection with a 95% resection margin zero. The median follow-up time was 22.5 months. The median progression-free survival (PFS) and overall survival (OS) were 23, 23.5 months, respectively. Conclusion: The preliminary data suggested good efficacy of the studied treatment design with acceptable adverse-event rates, however a larger multicentric phase 3 trial with a longer follow-up duration is recommended.

Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 286-286 ◽  
Author(s):  
Thomas Powles ◽  
Peter H. O'Donnell ◽  
Christophe Massard ◽  
Hendrik-Tobias Arkenau ◽  
Terence W. Friedlander ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Locally Advanced ◽  
Kidney Injury ◽  
Complete Response ◽  
Clinical Activity ◽  
Primary Endpoints ◽  
Duration Of Response ◽  
Visceral Metastases ◽  
Grade 3

286 Background: Anti-PD-L1 immunotherapy has shown promising clinical activity in urothelial carcinoma (UC). We report on a planned update of efficacy and follow-up in patients (pts) receiving durvalumab for the treatment of locally advanced or metastatic UC. Methods: Pts received durvalumab 10 mg/kg Q2W up to 12 months (mo), unacceptable toxicity or confirmed progressive disease. Tumor PD-L1 expression was assessed using the validated Ventana SP263 assay (PD-L1 high = TC ≥ 25% or IC ≥ 25%). Primary endpoints were confirmed ORR by RECIST v1.1 with blinded independent central review (BICR) and safety. Duration of response (DoR) and overall survival (OS) were key secondary endpoints. Results: As of July 24, 2016 (data cutoff [DCO]), the primary efficacy population included 103 pts who were followed for at least 13 weeks (median duration of follow up 7.3 mo); 37% had ≥ 2 prior regimens; 97% had prior platinum treatment; 95% had visceral metastases; and 49% had liver metastases at baseline. As of the DCO, 21 pts (20.4%) had a confirmed response per BICR (including 5 pts [4.9%] with a complete response) and an additional 3 pts had an unconfirmed response. Responses were seen in both PD-L1 high and PD-L1 low/negative subgroups (Table). Responses occurred early (median time to response 1.4 mo) and were durable. Median DoR has not been reached. Of the 21 confirmed responders, 18 pts had an ongoing response, 16 pts had DoR ≥ 6 mo and 7 pts had DoR ≥ 9 mo. Treatment-related Grade 3/4 AE rates were low (5.2%; as treated population, n = 191); Grade 3/4 immune-mediated AEs (imAEs) occurred in 3 pts, and 1 pt discontinued treatment due to an imAE of acute kidney injury. Conclusions: Durvalumab administered at 10 mg/kg Q2W showed clinical activity and an excellent safety profile in pts with locally advanced or metastatic UC. Clinical trial information: NCT01693562. [Table: see text]

Nintedanib + docetaxel in lung adenocarcinoma patients (pts) following treatment with immune checkpoint inhibitors (ICIs): Updated efficacy and safety results of the ongoing non-interventional study (NIS) VARGADO (NCT02392455).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9604-9604 ◽  
Author(s):  
Christian Grohé ◽  
Wolfgang Blau ◽  
Wolfgang Gleiber ◽  
Siegfried Haas ◽  
Stefan Krüger ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Clinical Decision ◽  
Interventional Study ◽  
Fgf Receptor ◽  
Grade 3 ◽  
Ecog Ps ◽  
Line Chemotherapy

9604 Background: Nintedanib (Vargatef) is an oral triple angiokinase inhibitor targeting VEGF-, PDGF- and FGF receptor pathways. It is approved in the EU and other countries in combination with docetaxel for treatment of locally advanced, metastatic or locally recurrent NSCLC of adenocarcinoma histology after 1st line chemotherapy. ICI +/- chemotherapy has changed the standard of care for 1st line treatment of metastatic non-mutated NSCLC. However, currently, only limited clinical data are available to help guide treatment decisions after prior ICI therapy in subsequent lines. Methods: This updated analysis is part of the ongoing NIS VARGADO (cohort B), a prospective non-interventional study of nintedanib + docetaxel after 1st line chemotherapy for adenocarcinoma NSCLC. The analysis includes 57 pts who had previously received both chemotherapy and ICI treatment. Results: Median age was 61 years (range: 45 – 80), 32/57 pts (56.1%) were men, and 41/57 pts (71.9%) were ECOG PS 0/1. 12/57 pts (21.1%) had brain metastases, and 46/57 pts (80.7 %) were current or former smokers. 1st line chemotherapy treatments included pemetrexed (36/57 pts, 63.2%), cisplatin (29/57 pts, 50.9%), carboplatin (33/57 pts, 57.9%), bevacizumab (14/57 pts, 24.6%), vinorelbine (13/57 pts, 22.8%), paclitaxel (8/57 pts, 14.0%), and docetaxel (1/57 pts, 1.8%). 2nd line treatments included nivolumab (34/57 pts, 59.7%), pembrolizumab (14/57 pts, 24.6%), and atezolizumab (7/57 pts, 12.3%). Under nintedanib and docetaxel, ORR was 50% (20/40 pts); DCR was 85.0% (34/40 pts). Median PFS was 6.5 months (95%CI 4.8 – 8.7), median OS was 12.4 months (95%CI 11.4 – 14.1). Treatment emergent adverse events (TEAEs) grade ≥3, serious TEAEs, and TEAEs leading to discontinuation were observed in 30/57 pts (52.6%), 30/57 pts (52.6%), and 17/57 pts (29.8%), respectively. Conclusions: This updated analysis of the VARGADO study continues to show the clinical benefit and manageable safety profile of nintedanib plus docetaxel in patients who had previously received both chemotherapy and ICI treatment. These data add to the real-world evidence that can inform clinical decision-making after prior ICI therapy. Clinical trial information: NCT02392455 .

Vinblastine, Mitoxantrone and Prednisone (MVP) Followed by Involved Field Radiotherapy (IF-XRT) for Early Clinical Stage Hodgkins’s Lymphoma: Long Term Follow-Up.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2677-2677
Author(s):  
Danielle Shafer ◽  
Hossein Borghaei ◽  
Michael Millenson ◽  
Nicos Nicolaou ◽  
Tahseen I. Al-Saleem ◽  
...  
Keyword(s):  
Overall Survival ◽  
Early Stage ◽  
Survival Rates ◽  
Complete Response ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Combined Modality Treatment ◽  
Grade 3

Abstract Background: The treatment of early stage Hodgkin’s lymphoma (HL) continues to evolve in attempt to improve the safety profile of the regimens and decrease their long-term toxicities. Treatment related mortality exceeds that from HL after 12 to 15 years. In light of the potential long-term complications associated with irradiation and chemotherapy, particularly pulmonary and cardiac toxicity, alternative approaches minimizing exposure to drugs with long-term organ toxicity have been examined. Objectives: We evaluated a novel regimen of MVP and IF-XRT for non-bulky early-stage HL. The primary outcomes were response rate and freedom from disease progression. Secondary outcomes were toxicity, specifically pulmonary and cardiac dysfunction. Methods: Patients were enrolled in this multi-site phase 2 study between 1995 and 1999. Eligible patients were 18 years of age or older, had ECOG performance status 0–2 and pathologically confirmed, clinically staged non-bulky Stage I or II HL. Patients received a minimum of four cycles of mitoxantrone 8mg/m2 and vinblastine 6 mg/m2 intravenously on days 1 and 15 of each 28-day cycle. Prednisone 100mg was given orally days 1 to 5 and 15 to 19. Chemotherapy was continued for two additional cycles after complete response, up to eight cycles. Patients then received IF-XRT (30.6 Gy-39.6 Gy) four weeks after completion of chemotherapy. G-CSF was not used as primary prophylaxis. Results: Thirty-four patients were evaluated for response in a final review. A total of 32 patients (94%) achieved a complete remission after combined therapy. Thirty patients (88%) achieved a complete response after chemotherapy alone. At a median follow-up of 49 months (range 16.9–79.7 months), 10 patients had relapsed, and three deaths were documented. None of the deaths occurred during treatment. The median time to progression was 30 months. The overall survival and disease-free survival rates at 5 years were 90% (95% confidence interval [CI], 73–97%) and 78% (95% CI, 58–89%), respectively. The treatment was well tolerated without significant grade 3/4 toxicity. (Grade 3/4 leukopenia 18% of patients; neutropenia 28%) There were no significant changes in DLCO or left ventricular ejection fraction at 12 months observed after chemotherapy. Twenty-one patients received only 4 cycles of chemotherapy; the median dose intensity for the entire group was 85%. Conclusions: As the management of early-stage HL continues to evolve in attempt to reduce long-term toxicity, this trial serves as a reminder of the balance required between efficacy and toxicity in this largely curable population. In this relatively well-tolerated regimen, there was minimal long-term toxicity, but a high number of relapses, most of which were successfully salvaged with resultant excellent 5-year overall survival rates. As the treatment for early-stage HL moves forward, there will undoubtedly be further attempts to modify the ABVD backbone. We await those results as well as long term data from the German Hodgkin Study group investigating reduction of combined modality treatment (HD10) in a similar patient population.

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.

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