Phase I trial of neoadjuvant chemoradiotherapy with capecitabine and weekly irinotecan followed by laparoscopic mesorectal excision

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14556-14556
Author(s):  
L. Ugidos ◽  
C. Conill ◽  
S. Delgado ◽  
A. Gines ◽  
R. Gallego ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Conformal Radiotherapy ◽  
Complete Response ◽  
Oncologic Outcomes ◽  
Mesorectal Excision ◽  
Grade 3

14556 Background: To establish the feasibility and efficacy of capecitabine with weekly irinotecan (CAPIRI) and concurrent radiotherapy (RT) in patients with locally advanced and resectable metastatic rectal cancer, followed by LAME. Methods: Eligible criteria included adenocarcinoma of the rectum staged by endoscopic ultrasonography (us), spiral abdominal and pelvic CT and chest X-ray. Patients received weekly irinotecan 50 mg/m2 (days 1,8,15,22,29) and two doses of capecitabine (days 1 through 5 for 5 weeks); dose level; (DL) I 250 mg/m2 bid; DL II 375 mg/m2 bid; DL III 500 mg/m2 bid, according to phase I methodology. Conformal radiotherapy was administered up to a total dose of 45 Gy/1.8 Gy per fraction. LAME was planned 5–7 weeks after CRT. Results: From January 2003 to March 2006, 22 patients (three with potentially resectable metastatic disease) were included. Median age was 62 (range 48 to 78). 6 pts were usT3N0 and 16 pts usT3–4N1. Seven patients were treated at DL I, six at DL II and nine at DL III. Grade 3 or 4 adverse events were observed in all levels; DL I asthenia (1p); DL II diarrhea (2p) and DL III asthenia and neutropenia (1p), diarrhea (1p) and hyperbilirrubinaemia (1p). All patients except one who refused treatment after 1 week therapy (DL I), completed CRT and underwent surgical resection (R0 81%, R2 19%). Abdominoperineal resection was done in two cases (9%). Conversion rate to open surgery was 5%. Median hospital stay was 7.9 days. The overall postoperative morbidity was 4.7%. Median excised nodes were 11 (range 4–21). Pathological complete response was observed in two patients (9%), both of them in DL III. With a median follow-up of 25 months (range 9–46), disease free survival and overall survival was 67% and 95% respectively. Conclusions: Preoperative CRT with CAPIRI is feasible, but severe adverse events were found in all levels despite the use of lower dose of capecitabine than previously published. LAME after CAPIRI had short oncologic outcomes comparable with open mesorectal excision. No significant financial relationships to disclose.

Multicenter, randomized phase II study of neoadjuvant pembrolizumab plus chemotherapy and chemoradiotherapy in esophageal adenocarcinoma (EAC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4005-4005
Author(s):  
Manish A. Shah ◽  
Khaldoun Almhanna ◽  
Syma Iqbal ◽  
Prashant Thakkar ◽  
Bryan J. Schneider ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Complete Response ◽  
Type I ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Grade 3

4005 Background: Recent transformative studies in the treatment of EAC support adjuvant nivolumab for patients with residual disease following neoadjuvant chemoradiotherapy (CRT) (Checkmate 577) and pembrolizumab (P) with chemotherapy in untreated metastatic disease (Keynote 590). We hypothesized that pre-operative P combined with CRT can further improve outcomes in patients with locally advanced EAC. Methods: Patients with cT3-4Nx or T2N1 M0 EAC or gastroesophageal junction (GEJ) adenocarcinoma eligible for curative surgery were randomized (1:1) to receive either full-dose paclitaxel (T)/ carboplatin (C) or T/C + P induction therapy. All patients then received CRT with weekly T/C, RT 41.4Gy in 23 fractions, and P every 3 weeks. Following resection, patients received P for one year. The primary endpoint is rate of major pathologic response (MPR), defined as pathologic complete response or near complete response ( < 10% residual cancer), with 80% power and 0.1 one-sided significance level to detect the difference between a MPR proportion of 30% (historical control) and an alternative hypothesis of 47% (with preoperative P). Tissue was collected for tumor immune microenvironment (TIME) analysis including bulk and single cell RNA(scRNA) expression analysis, DNA sequencing, and flow cytometry. Results: From 8/4/17 to 10/26/20, 40 patients were enrolled: median age 68 [38-81], male 32, esophagus/GEJ type I (n = 16), GEJ II/III (n = 24). CRT was well tolerated, with no grade 3-4 adverse events attributed to P. Notable toxicity included grade 3-4 pneumonitis (13%), anastomotic leak (13%), infection (35%). In 31 evaluable patients to date, the MPR rate was 50.0% (95% CI, 32.7%-67.3%). 1-yr disease free survival was 100% for patients with MPR vs. 31.8% without MPR, p = 0.002. Esophageal/GEJ type I cancers had a significantly higher MPR rate when compared with GEJ type II/III (76.9% vs 37.5%, p = 0.03). scRNA seq on > 100,000 tumor cells revealed EAC/GEJ type I had higher infiltration of activated dendritic cells (p = 0.12), whereas GEJ tumors have significantly higher infiltration of activated B cells (p = 0.02). Conclusions: The addition of P to preoperative CRT for EAC is safe and associated with a significantly higher MPR rate compared to historical data. We found MPR to be significantly enriched in EAC/GEJ type I tumors compared with GEJ II/III, associated with important differences in the baseline tumor immune microenvironment. Clinical trial information: NCT02998268.

Phase II study of perioperative toripalimab in combination with FLOT in patients with locally advanced resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4050-4050
Author(s):  
Hongli Li ◽  
Jingyu Deng ◽  
Shaohua Ge ◽  
Fenglin Zang ◽  
Le Zhang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Death Receptor ◽  
Disease Free Survival ◽  
Complete Response ◽  
R0 Resection ◽  
Combination Regimen

4050 Background: FLOT is the standard perioperative treatment for resectable gastric /gastroesophageal junction (GEJ) adenocarcinoma. However, patient’s outcome is still poor. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. This trial evaluates the addition of Toripalimab to FLOT for resectable patients. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥cT2 or cN+) were enrolled to receive 4 pre-and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2w). The primary endpoint was pathological complete response rate (pCR). The secondary endpoints included major pathological (complete and nearly complete) response (MPR), and R0-resection rate, 3-year disease-free survival rate, overall survival, and adverse events. Results: In total, of 36 patients were enrolled from June 2019 through Dec 2020. Male, 66.7%; median age, 60y; cT3 8.3%, T4, 83.3%; cN+ 88.9%; GEJ 47%; MSI-H, 5.6%, Her-2neu-positive, 5.6%, EBER-positive, 5.6%). Two patients refused surgery, six patients have not yet completely neoadjuvant treatment. 100% of patients completed the 4 pre-cycle. Patients who had received gastrectomy after neoadjuvant treatment (n=28) were included in this analysis. 6 (21%) patients had operations involving a thoracic approach (oesophagogastrectomy with two field lymphadenectomy), 21 (75%) gastrectomy with D2 lymphadenectomy. 8 (29%) evaluable patients had Clavien-Dindo grade II post-operative complications and 2 (7%) grade IIIA complications; one patient had an anastomotic leakage that was treated endoscopically. There were no emergency re-operations. All 28 patients achieved R0-resection and were discharged home after a median of 12 days (range:7-63) in hospital. 7 （25%）patients achieved pCR (TRG1a) and 12 (42.9%) patients achieved major pathologic response (MPR, TRG1a/b). Treatment-related adverse events (TRAEs) to any drug were reported in 30 (94%) patients. Mostly TRAEs were grade 1-2, the grade 3 or 4 TRAEs included neutropenia (34%), neutropenia (25%), lymphopenia (3%), Alanine aminotransferase increased (3%), hypokalemia (3%) and anaemia (3%). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate and well tolerated safety profile in patients with resectable gastric/GEJ adenocarcinoma. This combination regimen might present a new option for patients with locally advanced, resectable gastric/GEJ adenocarcinoma. Clinical trial information: NCT04354662.

Concomitant radical non-platinum radiochemotherapy for elderly patients with invasive bladder cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16135-e16135
Author(s):  
A. Rodica Maricela ◽  
L. N. Minea ◽  
X. Bacinschi ◽  
I. Isacu ◽  
A. Tarlea
Keyword(s):  
Bladder Cancer ◽  
Elderly Patients ◽  
Performance Status ◽  
Locally Advanced ◽  
Conformal Radiotherapy ◽  
Distant Metastases ◽  
Complete Response ◽  
Bladder Preservation ◽  
Cardiovascular Comorbidities ◽  
Grade 3

e16135 Background: Treatment of bladder cancer in elderly patients is a challenging problem because surgery is often not tolerable and the combination of extensive radiotherapy with chemotherapy is also difficult because of patients’ compliance and associated comorbidities. Our study evaluated concurrent radiochemotherapy in elderly patients with locally advanced bladder cancer (T2-T4) in terms of efficacy and tolerability. Methods: Between January 2005 and December 2007, we treated 34 patients with transitional carcinoma of the bladder, with or without nodal involvement, no distant metastases, and median age 79 years (range 66 - 89 years). Their performance status was 0–1-2 in 10–16–8 patients respectively. Cardiovascular comorbidities were the most common (15 patients). The treatment consisted in conformal radiotherapy (mean irradiation dose = 56.4 Gy) concomitant with biweekly Gemcitabine 200 mg/sqm starting on day 1 of radiotherapy. Results: Response was assessed at 4–6 weeks after the end of treatment by cystoscopy with biopsies and MRI. All the patients could end the intended radiation therapy but four of them could not tolerate all the chemotherapy. 13 patients achieved complete response, 12 patients - partial response and 9 patients stable disease. The most common toxicities were: diarrhea (grade 1–2 in 11 patients, grade 3–6 patients), cystitis (grade 1–2 in 5 patients), leucopenia (grade 1–2 in 12 patients, grade 3–4 in 2 patients), thrombocytopenia (grade 1–2 in 6 patients) and anemia (grade 1–2 in 4 patients). Three patient required hospitalization for dehydration and two for febrile neutropenia. After a median follow-up time of 17.4 months, there were 7 relapses and 5 distant metastases. One-year survival rate was 82.41% (28 patients). 6 patients died, 3 from their cancer and 3 from comorbidities. Conclusions: Chemoradiation is well enough tolerated even in elderly patients and also an efficient and organ sparing therapeutic alternative for patients over 65 years old. The treatment choice was based on patients’ preference considering better quality of life with bladder preservation. The use of age-specific therapy adjustments has shown that aggressive treatment for bladder cancer is associated with improved survival even in elderly patients. No significant financial relationships to disclose.

Phase Ib/II study of neoadjuvant chemoradiotherapy with CRLX101 and capecitabine for locally advanced rectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15144-e15144 ◽  
Author(s):  
Andrew Wang ◽  
Autumn Jackson McRee ◽  
A. William Blackstock ◽  
Bert H. O'Neil ◽  
Dominic T. Moore ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Ib ◽  
Grade 3

e15144 Background: There is strong interest in the development of novel agents to further improve the therapeutic ratio of neoadjuvant chemoradiotherapy for rectal cancer. CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. The purpose of this Phase Ib/II study is to assess toxicity and to evaluate whether the addition of CRLX101 to chemoradiotherapy can improve pathologic complete response (pCR) for rectal cancer. Methods: This is a single-arm multicenter Phase Ib/II study examining the addition of CRLX101 to a standard capecitabine-based chemoradiotherapy regimen. Phase Ib employs a 3+3 dose escalation design with starting dose of 12 mg/m2 every other week (QOW). Dose level +1 was 15 mg/m2 (MTD for CRLX101 single agent QOW). Upon reaching MTD for QOW dosing, protocol was modified to evaluate QW CRLX101 dosing starting at 12 mg/m2 and 15 mg/m2as +1 level. Secondary endpoints included pCR and clinical outcome. Results: A total of 32 patients were enrolled on the trial. 26/32 had T3-4, 9/32 had N2 and 16/32 had N1 disease. For QOW dosing, 9 patients completed treatment without DLT and MTD was identified as 15 mg/m2 QOW. 14 patients were treated on the Phase II portion of the study at 15 mg/m2 QOW prior to the initiation of weekly dosing Phase Ib cohorts. For QW dosing, 0/3 patients experienced DLT at 12 mg/m2 and 1/6 patients experienced DLT at 15 mg/m2. The DLT was skin desquamation requiring treatment delay. QW MTD was identified as 15 mg/m2. Toxicities (all grade 3 except lymphopenia) that could possibly be attributed to CRLX101 are in Table 1. Full clinical and pathologic staging were available for 29/32 patients. Mean neoadjuvant rectal (NAR) score was 19 with standard deviation of 15. At the weekly MTD, 3/6 patients had pCR. Conclusions: CRLX101 weekly at 15 mg/m2+ standard capecitabine-based chemoradiotherapy appears to be well tolerated, with promising pCR rates that warrants further evaluation. A larger PhII trial should be considered with this regimen. Clinical trial information: NCT02010567. [Table: see text]

scholarly journals Efficacy and Safety of Histone Deacetylase Inhibitors in Multiple Myeloma - a Systematic Review of Early Phase Clinical Trials

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5629-5629
Author(s):  
Sharoon Samuel ◽  
Muhammad Junaid Tariq ◽  
Muhammad Usman ◽  
Amna Khalid ◽  
Muhammad Asad Fraz ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Phase I ◽  
Hdac Inhibitors ◽  
Complete Response ◽  
Number Of Patients ◽  
Grade 3 ◽  
Early Phase Clinical Trials

Abstract Introduction Recent studies in novel therapies have created opportunities for new treatment regimens to be used in the management of multiple myeloma. Histone deacetylase (HDAC) inhibitors lead to epigenetic manipulation of multiple myeloma (MM) cells by reducing resistance to pro-apoptotic signals. Panobinostat is an FDA approved HDAC inhibitor for multiple myeloma. The aim of this article is to study the safety, efficacy and dose limiting toxicities of HDAC inhibitors in the early phase clinical trials in multiple myeloma. Methods We performed a comprehensive literature search for phase I & I/II trials of HDAC inhibitors during last ten years using following databases: PubMed, Embase, AdisInsight, and Clinicaltrials.gov. Studies involving HDAC inhibitors in multiple myeloma other than panobinostat irrespective of the age, sex or specific eligibility criteria were included. Results Out of 2537 studies, we included 25 trials (23 phase I, 2 phase I/II) of HDAC inhibitors in this systematic review having a total of 518 patients. Of these, 471(90.9%) patients were evaluable for response. Vorinostat (Vor) is the most studied drug used in 13 trials (n=281). Two trials had Vor-only regimen and the remaining 11 had combination regimens mostly with lenalidomide and bortezomib. Vor, in combination with lenalidomide (R), bortezomib (V) and dexamethasone (d) has showed 100% overall response rate (ORR) in 30 newly diagnosed multiple myeloma (NDMM) patients, (Kaufmann et al., 2016), fifty two percent patients achieved very good partial response (VGPR) and 28% patients showed complete response (CR). Another study using Vor + R regimen after autologous stem cell transplant in 16 NDMM patients showed VGPR in 7, stringent complete response (sCR) in 4, partial response (PR) in 2 and CR in 3 patients (Sborov et al.). Grade 3 neutropenia was seen in 1 patient in this study. Richter et al, 2011 showed an ORR of 24% in 29 relapsed refractory multiple myeloma (RRMM) patients with Vor only regimen. Another study (Kaufmann et al., 2012) with Vor only regimen used in 10 RRMM patients showed stable disease (SD) in 9 and minimal response (MR) in 1 patient. ORR of 65% was achieved in 31 RRMM patients receiving Vor in combination with doxorubicin & bortezomib (Vorhees et al, 2017). Thrombocytopenia & neutropenia were reported in 94% and 59% patients respectively. Ricolinostat in combination with Rd and Vd achieved an ORR of 55% and 29% respectively in two studies with 38 and 57 evaluable patients (NCT01583283, NCT01323751). Another ricolinostat regimen with pomalidomide & dexamethasone achieved ≥PR in 6/11 RRMM patients (Madan et al., 2016). Table 1 illustrates the efficacy, number of patients and regimens used in all the studies in this systematic review. Quisinostat in a 2017 study by Moreau P et al. (NCT01464112) showed an ORR of 88% in a combination regimen with Vd in RRMM patients (N=18). Drug related adverse events were seen in 13 patients, thrombocytopenia being most common in 11 patients, 2 patients had grade 3 cardiac disorders and 1 patient had a cardiac arrest. Romidepsin in a phase I/II study (Harrison et al., 2011) combined with Vd was used in 25 RRMM patients. ORR was 60% with VGPR n=7, CR n=2, PR n=6, SD n=5 and PD n=1. Grade ≥3 thrombocytopenia in 16, neutropenia in 9 and peripheral neuropathy in 2 patients was seen. Popat et al used combination of two HDAC inhibitors CHR 3996 and tosedostat in 20 RRMM patients. ORR was 10% and SD was seen in 30% patients. Grade 3/4 toxicities seen were thrombocytopenia (n=12), leukopenia (n=6) and diarrhea (n=5). A phase I study on AR-42 drug in 17 RRMM patients (Sborov et al., 2017) showed SD in 10, PD in 4, MR in 3 patients with progression free survival (PFS) of 8.2 months. Thrombocytopenia, neutropenia and lymphopenia were seen in 11, 10 and 6 patients respectively. A detail of all grade 3 and higher adverse events along with dose limiting toxicity is given in table 2. Three trials (NCT02576496, NCT01947140, NCT03051841) of Edo-S101, romidepsin and CKD-581 are currently recruiting with 84, 93 and 18 planned number of patients. Conclusion Regimens containing vorinostat have shown an ORR up to 100% in NDMM patients. HDAC inhibitors have also shown promising efficacy up to 88% ORR in RRMM population. Majority of the patients developed cytopenias as hematological adverse events. Disclosures No relevant conflicts of interest to declare.

Phase I study of capecitabine combined with weekly carboplatin and intensity modulated radiation therapy (IMRT) for treatment of locally advanced squamous cell carcinomas of the head and neck (HNSCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15522-15522
Author(s):  
C. Y. Thomas ◽  
P. Read ◽  
K. Sheng ◽  
D. Bliesner ◽  
P. Levine ◽  
...  
Keyword(s):  
Phase I ◽  
Locally Advanced ◽  
Intensity Modulated Radiation Therapy ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Stage Iii ◽  
Fixed Dose ◽  
Parotid Sparing ◽  
Grade 3 ◽  
Carboplatin Auc

15522 Background: Chemoradiotherapy (CRT) programs for locally advanced HNSCC that reduce toxicity but maintain efficacy are needed. Methods: A two-step phase I trial to determine the maximum tolerated dose (MTD) of capecitabine combined with fixed dose carboplatin, given prior to and during concomitant IMRT. Start dose of capecitabine =1500 mg/m2/d p.o. BID days 1–14 and 22–35 with carboplatin AUC =2 IV weekly x 6. With IMRT, the doses were adjusted to 1000 mg/m2/d and AUC =1.5, respectively. Parotid-sparing IMRT = 50 and 45 Gy/25 fractions to gross disease (GD) and low risk nodes, respectively; 3D conformal boost of 20 Gy/10 fractions to GD. Dose limiting toxicity (DLT) defined as ANC <750, ≥ grade 3/4 thrombocytopenia or selected non-hematologic toxicities. Results: 11 patients (pts) with stage III/IV (T2–4,N1–2C) HNSCCs of the oropharynx (7), oral cavity (2), both (1), or hypopharynx (1) were studied. 10/9 pts evaluable for toxicity after induction/concomitant chemotherapy, respectively; 2 pts had early disease progression (d22 and 43). During radiation, the MTD for capecitabine established as 825 mg/m2/d. At start dose, 2/3 pts developed thrombocytopenia as DLT; CRT-related toxicities = grade 3 mucositis (3), dysphagia (3), fatigue (1), anemia (1), and dermatitis (1). For induction chemotherapy, DLTs seen in 0/3 pts at capecitabine =1750 mg/m2 and 1/6 at lower doses (grade 4 diarrhea; no other Gr3/4 drug-related toxicities). Response of primary (or neck) tumors to induction: CR 3 (3), PR 6 (3), SD 1 (3), and PD 2 (2). After CRT, 8/9 pts achieved CR and are alive without disease (mean follow-up 6 months). Conclusions: Capecitabine 825 mg/ m2/d and carboplatin AUC =1.5 weekly given on the described schedule and in combination with IMRT produce moderate toxicity and a high complete response rate in stage III/IV HNSCC pts that received the same drugs as induction therapy. The latter combination was also well tolerated and had anti-tumor activity (capecitabine Y=1500–1750 mg/m2/d). Additional studies are warranted to determine if these regimens provide an effective but less toxic alternative to cisplatin or taxane-based CRT programs. Supported in part by Bristol-Myers-Squibb. No significant financial relationships to disclose.

Phase II open clinical trial to evaluate efficacy and safety of neoadjuvant trastuzumab in HER2-positive locally advanced breast cancer (LABC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 592-592
Author(s):  
C. H. Arce-Salinas ◽  
F. U. Lara ◽  
E. Leon
Keyword(s):  
Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Her2 Positive ◽  
Primary Systemic Therapy ◽  
Her 2 ◽  
Grade 3

592 Background: LABC in Mexico represents between 50–60% of the new diagnosed cases, and 25–30% of those cancers are HER-2/neu positive. Primary systemic therapy trastuzumab-based combination chemotherapy (ChT) has shown clinical benefit and pathologic complete response rates are obtained between 17%-67%. The aim of this study was evaluate the complete pathologic response (pR) rate with the combination of four cyles of FAC (5FU/Doxorubicin/Cyclophosphamide) followed by weekly paclitaxel (PTX) and trastuzumab. As secondary endpoint was evaluate cardiac safety. Methods: All patients with LABC HER-2 positive (IHC 3+ or FISH amplification) with stages IIb-IIIc were included, patients with palpable nodes underwent fine needle aspiration to confirm metastatic nodal disease (MND), other inclusion criteria was FEVI ≥55% determined by MUGA, hematologic, renal and hepatic function normal. We exclude inflammatory breast cancer. All patients received 4 cycles of FAC followed by weekly PTX (80 mg/m2) concomitantly with trastuzumab, 2 mg/kg, at the end of treatment surgery was performed, and pR was evaluable. Complete pR was defined as the absence of tumor cells in breast and axillary nodes. Disease free survival (DFS) was calculated with Kaplan-Meier method. Protocol was approved by local ethical committee. NCT 00533936. Results: We included 92 patients, median age was 48 (27–68) yrs. Median tumor size was 6 (5.4–6.5) cm, 84.9% had MND. Efficacy analysis was made in 71 patients; 21 patients are still under treatment. Overall clinical response was reached in 71% (complete 37% and partial 42%). Eleven patients were considered inoperable (skin affection, larger size > 5 cm or fixed to chest wall and received radiotherapy 50 Gy). Complete pR was reported in 48% of cases. Median follow-up was 17.4 (CI95% 14.9, 17.6) mo and media of DFS was 25.1 (CI95% 23.5, 26.7) mo. We found cardiac toxicity (CT) grade 3 in 1.1%, and grade 2 in 3.2%. Conclusions: Combination of PTX and trastuzumab after 4 cycles of FAC is highly active in terms of complete pR. This scheme was tolerated, with CT grade 3–4 in less than 2%. No significant financial relationships to disclose.

Induction chemotherapy (CT) with docetaxel, cisplatin, and fluorouracil (TPF) followed by concomitant cisplatin plus radiotherapy in locally advanced nasopharyngeal cancer (NPC): Results after 06 years.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6075-6075
Author(s):  
Esma Kerboua ◽  
Kamel Bouzid
Keyword(s):  
Stable Disease ◽  
Therapeutic Option ◽  
Locally Advanced ◽  
Nasopharyngeal Cancer ◽  
Clinical Signs ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Complete Response ◽  
High Stage ◽  
Grade 3

6075 Background: In squamous cell carcinoma of head and neck cancer, TPF induction CT improved survival over cisplatin plus fluorouracil (Posner MR: NEJM, vol357, Oct 2007). The main objective of this study is to evaluate the activity and safety of TPF in patients (pts) with locally advanced NPC followed by concomitant cisplatin plus radiotherapy (cCTRT). Methods: Pts with undifferentiated NPC were enrolled from December 2006–December 2012 and received 3 cycles of TPF (docetaxel 75 mg/m2 and cisplatin 75/m2 day 1, plus fluorouracil 750 mg/m2 days 1–5, every 4 wks) with G-CSF days 1–5 post CT. CT was followed by cCTRT with cisplatin 40 mg/m2/wk and radiotherapy (65–70 Gy) starting 4–6 wks after the third cycle of CT. The primary endpoint was overall response rate (ORR) after induction CT and after cCTRT. Secondary end points were safety, disease free survival (DFS), and overall survival (OS). Results: 42 pts have been enrolled (26 M/16 F). UICC 1997 classification: n=9 stage II, n=10 stage III, n=23 stage IV. Median age is 37 yrs (range 18–64). Evocative clinical signs are cervical nodes n=20, rhinologic n=13, otologic n=5, and neurologic n=4. All pts were evaluated for safety and 38 for response.TPF well tolerated with main toxicities grade 3–4 (WHO) were neutropenia 36%, thrombocytopenia 32%, anemia 18%, diarrhea 6%, and mucositis 18%. Four pt died from sepsis that was probably treatment-related. ORR was 90% with an 71.4% (n=27) complete response (CR) rate, 23.6% (n=9) partial response (PR), and 5.2% (n=2) stable disease. No pts progressed after induction CT. Main toxicity during cCTRT was neutropenia grade 3–4 in 9%, mucositis grade 3 in 45% and grade 4 in 4%. Late toxicities were xerostomia grade 3 in 50%. At treatment completion, CR and PR rates were 79% and 20%; 2 pts had stable disease. At a median follow up of 72 months (range 7–72), 8% of pts have shown recurrence or progressive disease. DFS and OS rates at 72 months were 65% and 70%, respectively. Conclusions: TPF followed by cCTRT appears to be an active and feasible regimen with a manageable safety profile and may be a promising therapeutic option for pts with high stage NPC.

A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (MEDI4736) as preoperative treatment in rectal cancer: PANDORA study first-stage.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3607-3607
Author(s):  
Stefano Tamberi ◽  
Elisa Grassi ◽  
Jody Corbelli ◽  
Giorgio Papiani ◽  
Maria aurelia Barbera ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adverse Events ◽  
Neoadjuvant Therapy ◽  
Phase Ii ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Preoperative Treatment ◽  
Open Label ◽  
Multi Centre Study ◽  
Grade 3

3607 Background: The combination of capecitabine plus long course radiotherapy (RT) is the standard preoperative therapy in cT3-4 cN+ rectal cancer. Pathologic Complete remission (pCR) can be considered as surrogate end point of efficacy of treatment in terms of disease free survival (DFS). Preclinical data points heavily toward a strong synergy between RT and immune treatments. Methods: This is a prospective phase II, open label, single arm, multi-centre study, conducted with support from AstraZeneca, in patient with locally advanced rectal cancer who receive concomitant CT/RT therapy (825 mg/m2 twice daily capecitabine every day and 5040 cGy radiotherapy for 5 days per week for 5 weeks) followed by durvalumab (1500 mg Q4W for 3 administrations). Surgery is performed after 10-12 weeks from neoadjuvant therapy. The primary endpoint is pCR rate after at least 1 cycle of durvalumab. The sample size has been estimated by using the optimal Simon’s two-stage design. If more than 4 complete responses are observed in the first 19 enrolled patients, 36 additional patients will be accrued for a total of 55 evaluable patients. Results: Between November 2019 and July 2020, 20 patients were accrued and 19 were evaluable for study objectives, concluding the first stage of the trial. Baseline characteristics of the first 19 evaluable patients enrolled are listed in the table. All patients received 3 infusions of durvalumab; 18 patients underwent surgery after a median of 13 weeks from CHT/RT end. Five complete pathological responses (ypT0N0) were observed, allowing to proceed to the second stage. About toxicity, four patients had Grade 3-4 adverse events (AE); the most frequent G3-4 AE related to the neoadjuvant therapy were anemia (n=1), diarrhea (n=2) and neuthropenia (n=2). No grade 3 and 4 adverse events related to Durvalumab treatment were observed. Eight patients had G1-2 AE related to durvalumab, the most common being asthenia (n=2) and nausea (n=2). Conclusions: At the end of study’s first stage the preoperative treatment with radiotherapy plus capecitabine followed by durvalumab showed a safe toxicity profile and promising activity in terms of pCR rate. The second part of the trial is ongoing, and the accrual is under completion (44 patients enrolled as of 10 February 2021). Clinical trial information: NCT04083365. [Table: see text]

Phase I results of the randomized, placebo controlled, phase I/II study of the novel oral c-Met inhibitor, ARQ 197, irinotecan (CPT-11), and cetuximab (C) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC) who have received front-line systemic therapy.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 527-527 ◽  
Author(s):  
C. Eng ◽  
J. C. Bendell ◽  
A. Bessudo ◽  
N. Y. Gabrail ◽  
J. Diamond ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Complete Response ◽  
Ecog Performance Status ◽  
Tumor Cell Migration ◽  
Arq 197 ◽  
Grade 3

527 Background: ARQ 197 selectively inhibits the c-Met receptor tyrosine kinase (RTK), which has been implicated in tumor cell migration, invasion, proliferation, and angiogenesis. CPT-11 plus C is a standard of care for CPT-11-refractory mCRC pts with WT KRAS tumors. Resistance to C has been associated with activation of alternative RTK pathways including c-Met. We hypothesize that adding ARQ 197 to CPT-11 plus C may decrease resistance to C therapy and improve pt outcomes. Methods: The primary objectives of phase I were to evaluate safety and tolerability of ARQ 197 administered in combination with CPT-11 plus C, and to define a recommended phase II dose (RPTD). Pts with surgically unresectable locally advanced or mCRC who received at least 1 prior line of chemotherapy, KRAS WT and ECOG performance status < 2 were eligible. Cohorts of 3 pts each were treated with CPT-11 (180 mg/m2) and C (500 mg/m2) every 2 weeks along with escalating doses of ARQ 197 (120, 240, 360 mg) PO BID. Blood and tissue were collected for PK, biomarker, and other analyses. If no DLTs were observed during the first 28-day cycle in 3 pts treated in cohort 3, 360 mg BID would be defined as the RPTD. Responses were assessed every 8 weeks per RECIST v1.1. Results: Nine pts were treated in 3 cohorts. Median age: 53 yrs (range 30-77); ECOG PS 0/1: 4/5; median prior therapies: 2 (range 1-4). No DLTs were observed. The RPTD for ARQ 197 was 360 mg BID. To date, two pts have discontinued (1 disease progression and 1 withdrew consent after achieving complete response) and 7 pts remain on study. The reported grade 3/4 adverse events were: neutropenia (3/4: 1/1), and one case each of grade 3 fatigue, leucopenia, acneiform rash, vomiting, anemia and syncope. Preliminary efficacy data in 9 evaluable pts include 1 CR (after 4 cycles), 2 PR (after 2 cycles), 5 SD, and 1 PD as best response. Conclusions: The combination of ARQ 197 and CPT-11 plus C was well tolerated with encouraging preliminary antitumor activity. The RPTD for ARQ 197 was 360 mg BID. The randomized phase II portion of the study continues accrual. [Table: see text]

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