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.

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.

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.

A phase II study of preoperative docetaxel, cisplatin, and capecitabine in patients with gastric carcinoma.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 89-89 ◽  
Author(s):  
Pei-Jye Voon ◽  
Mu-Yar Soe ◽  
Ying Kiat Zee ◽  
Benjamin Chuah ◽  
Robert S. C. Lim ◽  
...  
Keyword(s):  
Gastric Adenocarcinoma ◽  
Phase Ii ◽  
Locally Advanced ◽  
Postoperative Mortality ◽  
Complete Response ◽  
Pathological Response ◽  
Perioperative Chemotherapy ◽  
Advanced Gastric Adenocarcinoma ◽  
Grade 3 ◽  
Dose Modifications

89 Background: Perioperative chemotherapy has been shown to improve outcomes among patients with locally advanced gastric adenocarcinoma. As docetaxel (D), cisplatin (C), and capecitabine (X) are active agents in gastric adenocarcinoma, we conducted a phase II trial to assess the efficacy and tolerability of preoperative DCX in patients with gastric adenocarcinoma. Methods: We enrolled patients with locally advanced gastric adenocarcinoma (clinical T3/4 or N positive) to preoperative DCX repeated every 21 days for three cycles, followed by surgery. The first cohort of 10 patients received docetaxel 35 mg/m2, cisplatin 35mg/m2 on days 1 and 8, with capecitabine 750 mg/m2 twice daily from day 1 to day 14. A subsequent cohort of another 11 patients had dose modifications for docetaxel and cisplatin, both to 30mg/ m2 on days 1 and 8. Results: Twenty-one patients were recruited. Median age was 61 years. Seventy-one percent of patients completed a total of 3 cycles of planned chemotherapy. Fourteen patients have successfully undergone surgery. R0 resection rate was 88%. Pathological complete response (pCR) and near complete response (pnCR) were both 17%. Preoperative radiological assessment showed a partial response rate of 65% after 2 cycles of treatment. Good pathological response (pCR and pnCR) was associated with better event-free survival (26 months vs 12 months, p=0.031). Common grade 3/4 toxicities were diarrhea (38%), neutropenia (30%), stomatitis (14%) and hypokalemia (14%). However, the diarrhea rate was reduced to 15% with dose modifications as mentioned above after 50% of the first cohort of 10 patients developed grade 3/4 diarrhea during the first cycle of chemotherapy. Febrile neutropenia rate was 14%. There was one treatment related death before surgery but no postoperative mortality. Conclusions: Preoperative DCX is highly active with modest toxicity in locally advanced gastric adenocarcinoma. DCX represents an attractive alternative regimen without the need for protracted infusional drug in perioperative chemotherapy for patients with locally advanced gastric adenocarcinoma. Good pathological response is associated with better outcome.

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.

EORTC 24051: Unexpected side effects of a phase I study of TPF induction chemotherapy (IC) followed by chemoradiation (CRT) with lapatinib (LAP), a dual EGFR/ErbB2 inhibitor, in patients with locally advanced larynx and hypopharynx squamous cell carcinoma (LA-LxHxSCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6017-6017
Author(s):  
P. M. Specenier ◽  
Y. Lalami ◽  
J. Vermorken ◽  
D. Lacombe ◽  
I. El-Hariry ◽  
...  
Keyword(s):  
Dose Level ◽  
Renal Toxicity ◽  
Locally Advanced ◽  
Treatment Interruption ◽  
Safety Issues ◽  
Male Patients ◽  
Level 1 ◽  
Grade 3

6017 Background: CRT is considered a standard approach for LA-LxHxSCC. TPF IC regimen seems to improve outcome in locally advanced head and neck SCC. The addition of LAP was investigated in combination with a sequential therapeutic approach (IC→ CRT). Methods: Eligible tumors were SCCHN: T3-T4 larynx (Lx), T2-T4 hypopharynx (Hx) N0–3 M0. The objective of this trial is to determine MTD, DLT and recommended dose of LAP when administered with TPF IC (docetaxel (T) 75mg/m2 (60 mg/m2 for the first cycle) d1, CDDP 75mg/m2 d1, 5FU 750mg/m2/d continuous infusion d1-d5 q3weeks) followed by CRT (weekly carboplatin AUC 1.5 and RT 70Gy in 7 weeks; 2Gy/fx). LAP is administered concomitantly with IC (escalating dose 500–1500mg po daily) and during CRT (1,500 mg daily). Results: Seven male patients were included; tumor sites: LX (n = 3) / Hx: (n = 4), median age 59 years (range: 47–79), WHO PS 0–1, no severe or uncontrolled comorbidity. Three pts were included in the first cohort, at dose level 1 (LAP 500 mg daily plus TPF IC). Renal toxicity was observed among these 3 pts (grade 4 [n = 1], grade 2 [n=1] and grade 1 [n=1]), with 1 DLT, leading to treatment interruption in this group. This nephrotoxicity was reversible after stopping lapatinib and hydration of the patients. As LAP plus cisplatinum plus RT was feasible in another study, a second cohort was conducted in 4 pts, receiving LAP at the same dosage, and docetaxel (T) was only introduced from cycle 2 of IC to see what is the role of T in the observed side effect. Two DLTs were observed among this second cohort of subjects: one pt presented a grade 2 renal toxicity, grade 3 diarrhea and dehydration and a second pt presented a grade 3 anorexia and grade 3 stomatitis. Based on the occurrence of 3 DLTs at the first dose level of LAP, patient recruitment was closed. Despite these safety issues, all patients recovered and were treated off-study. They will receive follow-up as foreseen by the protocol. Conclusions: These data suggest that LAP should not be combined with TPF IC regimen for LA-LxHxSCC due to prohibited toxicity. [Table: see text]

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]

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]

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]

Daratumumab (DARA) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients (pts) with newly diagnosed multiple myeloma (MMY1001): An open-label, phase 1b study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8000-8000 ◽  
Author(s):  
Andrzej J. Jakubowiak ◽  
Ajai Chari ◽  
Sagar Lonial ◽  
Brendan M. Weiss ◽  
Raymond L. Comenzo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Safety Profile ◽  
Standard Of Care ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Open Label ◽  
Frontline Treatment ◽  
Grade 3

8000 Background: DARA in combination with established standard of care regimens prolongs PFS, deepens responses, and demonstrates a favorable safety profile in relapsed or refractory multiple myeloma (MM). The tolerability and efficacy of DARA-KRd in newly diagnosed MM pts was examined. Methods: Newly diagnosed pts regardless of transplantation eligibility were enrolled. Pts received DARA 16 mg/kg QW for Cycles 1-2, Q2W for Cycles 3-6, and Q4W thereafter. All pts received the 1st dose of DARA split over 2 days. Carfilzomib (K) was administered on Days 1, 8 and 15 of each 28-day cycle (20 mg/m2 on C1D1, 36 or 70 mg/m2 subsequently based on tolerability of first dose) for ≤13 cycles or elective discontinuation for ASCT. Lenalidomide 25 mg was given on Days 1-21 and dexamethasone 20-40 mg per week. The primary endpoint was tolerability. Results: Twenty-two pts (median [range] age, 60 [34-74] y) were enrolled and received a median of 8 (1-10) treatment cycles. Nineteen pts escalated K dose to 70 mg/m2 by C1D15. Median (range) duration of follow-up was 7.4 (4.0-9.3) months. Six (27%) pts discontinued treatment (1 AE [pulmonary embolism]; 1 PD; 4 other [ASCT]). Serious AEs occurred in 46% of pts, and 14% were possibly related to DARA; 18 (82%) experienced a grade 3/4 TEAE. The most common grade 3/4 TEAEs (>10%) were lymphopenia (50%) and neutropenia (23%); 1 (5%) cardiac grade 3 TEAE was observed (congestive heart failure) which resolved; pt quickly resumed study treatment with reduced K dose. No grade 5 TEAE was reported. All DARA-associated infusion reactions (27% of pts) were grade ≤2. Treatment with DARA-KRd yielded an ORR (≥partial response) of 100% (5% complete response, 86% ≥very good partial response) in 21 response-evaluable pts. The 6-month PFS rate was 100%. Conclusions: The addition of DARA to KRd was well tolerated; the overall safety profile was consistent with that previously reported for KRd, with no additional toxicity observed with the addition of DARA. Deep and durable responses were observed. These data support further investigation of DARA-KRd as a frontline treatment regimen. Updated data will be presented based on longer follow up. Clinical trial information: NCT01998971.

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