Docetaxel, oxaliplatin, and capecitabine (TEX regimen) for patients with metastatic gastric cancer: Interim results from a phase II trial by the German AIO Group

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4554-4554 ◽  
Author(s):  
M. H. Moehler ◽  
P. Thuss-Patience ◽  
D. Arnold ◽  
W. Grothe ◽  
A. Stein ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Response Assessment ◽  
Metastatic Gastric Cancer ◽  
Phase Ii Trials ◽  
Grade 3 ◽  
Ecog Ps

4554 Background: Combination regimens of 3 drugs have shown promising activity as treatment for patients (pts) with metastatic gastric cancer (GC). Docetaxel combined with cisplatin and 5-FU (CF) improved overall survival and response rates when compared to standard CF. However, the identification of less toxic and more convenient variants of this regimen is still important. We have previously established a regimen with docetaxel (T) combined with oxaliplatin (E) and capecitabine (X) in a phase I trial [Grothe et al., Proc. ASCO 2006]. Results of a preplanned interim analysis of subsequent multicenter phase II trials of the TEX regimen are presented here. Methods: Pts with metastatic or locally advanced GC, adequate organ function, ECOG PS 0–2, and no prior chemotherapy for advanced disease (adjuvant allowed) were enrolled. TEX regimen was administered as defined: T 35 mg/m2 and E 70 mg/m2 on days (d) 1 and 8, with X 800 mg/m2 bid on d1–14 every 22 days Toxicity assessment was done 3-weekly while CT scans were repeated 9-weekly. Results: 35 of 48 pts were enrolled until 06/08: 28 male / 7 female, median age 59 (36–81) years, ECOG PS 0/1/2 69%/31%/0%, gastric / gastroesophageal cancer 60%/40%, distant metastases 96%, tumor in situ 37%. The most common toxicities reported were (CTC grade [gr] 3/4): diarrhea 20%/3%, vomiting 11%/3%, asthenia and neurotoxicity each 9%/0%. Mucositis and hand-foot-syndrome were observed in (grade 1+2 / grade 3) 29%/0% and 26%/3%, respectively. Hematoxicity was mild with grade 3 anemia in 10% and no other grade 3/4 toxicity except one episode of febrile neutropenia . Of 25 pts evaluable so far, first tumor response assessment revealed (RECIST criteria) partial response in 36% and stable disease in 40% of patients. Conclusions: TEX is a safe and tolerable regimen for patients with metastatic gastric cancer. Preliminary efficacy results indicate promising activity. Mature data including progression free survival will be presented at the meeting. [Table: see text]

Docetaxel, oxaliplatin, and capecitabine (DOX) combination chemotherapy for metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15065-e15065 ◽  
Author(s):  
Luigi Di Lauro ◽  
Domenico Sergi ◽  
Franca Belli ◽  
Silvia Ileana Fattoruso ◽  
Maria Grazia Arena ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Combination Chemotherapy ◽  
Gastroesophageal Junction ◽  
Distant Metastases ◽  
Metastatic Gastric Cancer ◽  
Secondary Prophylaxis ◽  
Stage Design ◽  
Grade 3 ◽  
Ecog Ps ◽  
Disease Location

e15065 Background: So far, the prognosis of advanced gastric cancer is dismal. Combination chemotherapy of docetaxel (D), cisplatin (C) and fluorouracil (F) showed activity in metastatic gastric cancer, but this regimen was complicated by a high incidence of myelotoxicity. We performed a multicenter phase II trial substituting C with oxaliplatin (O) and F with capecitabine (X) in chemotherapy-naive patients (pts) with gastric or GEJ adenocarcinoma. Methods: Pts with measurable distant metastases received D 60 mg/mq iv, O 100 mg/mq iv on day 1 and X 500 mg/mq orally twice daily continuously, with cycles repeated every 3 weeks for a maximum of 8. G-CSF was used only as secondary prophylaxis. The primary endpoint was overall response rate (RR) according to RECIST. Toxicity was reported according to NCI-CTC v 3.0. Optimal Simon's two-stage design was employed with 6/15 responses required in the first stage to allow continuation to 46 pts. Results: 46 pts were enrolled: M/F 28/18; median age 66 years (32-75); median ECOG PS 1 (0-2); primary tumor resected/ unresected 16/30; disease location was gastric in 34 and GEJ in 12 pts; sites of disease were liver in 27, nodes in 25, peritoneum in 20, lung in 8 and bone in 5 pts. At the time of analysis all pts were evaluable for response and toxicity. In 46 pts, 3 CR and 21 PR were observed, for an overall RR of 52.1% (95% CI, 37.7%-66.5%). Responses were obtained in 15/27 pts (55%) with liver metastases. Disease remained stable in 14 pts (30.5 %). Median TTP was 6.8 months and median OS was 12.6 months. Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 41%, 4% and 9% of the pts, respectively. Febrile neutropenia was observed in 2 pts (4%). Other grade 3 toxicities included mucositis in 2 pts (4%), vomiting in 3 pts (6.5%) and diarrhea in 2 pt (4%). There were no severe neurotoxicity, nor treatment-related deaths. Conclusions: The DOX combination is an active and well tolerated novel chemotherapy regimen for treating metastatic gastric or GEJ adenocarcinoma and deserves further evaluation in randomized trials and, hopefully, in neoadjuvant setting.

EXIBIT: An international multicenter phase II trial of gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4135-4135 ◽  
Author(s):  
T. André ◽  
J. M. Reyes-Vidal ◽  
L. Fartoux ◽  
P. Ross ◽  
M. Leslie ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Bile Ducts ◽  
Locally Advanced ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Extrahepatic Bile Ducts ◽  
Grade 3 ◽  
Ecog Ps

4135 Background: Biliary tract carcinomas (BTC) are often diagnosed at an advanced/metastatic stage and have a poor prognosis. The combination of gemcitabine and oxaliplatin (GEMOX) showed promising activity in a French Phase II study (4 centers) in advanced BTC (André. Ann Oncol 2004;15:1339–1343). The objective of this study is to further evaluate the efficacy and safety of GEMOX as first-line therapy in patients (pts) with advanced BTC. Methods: Eligible pts were >18 years of age with histologically proven and measurable, locally advanced or metastatic BTC, had an ECOG PS ≤ 2, adequate renal and hematologic functions, bilirubin < 2.5 × upper limit of normal, and no prior malignancy or brain metastases. Gemcitabine 1000 mg/m2 (Day 1) and oxaliplatin 100 mg/m2 (Day 2) were administered every 2 weeks. The primary objective was response rate (RR) by RECIST (one dimension); secondary objectives were progression-free survival (PFS), overall survival (OS), and safety. Here we report an interim analysis of OS and safety. Results: A total of 70 pts were enrolled between April 2003 and April 2005. The median age was 62 years (range 30–83), 40.0% of pts were male, 94.3% had ECOG PS 0–1. Tumor sites were intrahepatic bile ducts (37.1%), gallbladder (31.4%), extrahepatic bile ducts (12.9%), ampulla of Vater (1.4%), intra/extrahepatic bile ducts (1.4%), missing data (15.7%); 98.6% of pts had no prior radiotherapy and 50% had no prior surgery for BTC. Median OS is 8.25 months (68% of pts are dead and 32% have censored data). Sixty-seven pts were evaluable for safety. Grade 3/4 (NCI-CTC v. 2) hematologic toxicities (% of pts) included thrombocytopenia 10.4%, anemia 9.0%, and neutropenia 9.0%. One pt had febrile neutropenia. Grade 3/4 nonhematologic toxicities included pain 10.4%, ALT elevation 9.0%, fatigue 9.0%, infection 10.4%, vomiting 9.0%, sensory neuropathy 4.5%, nausea 4.5%, and diarrhea 3.0%. One patient died during treatment (cause unknown). Conclusions: GEMOX has acceptable toxicity in pts with BTC. Updated efficacy data (RR, PFS, and OS for the entire population and also by tumor sites) will be presented at the meeting. [Table: see text]

Randomized phase II study of PEP02, irinotecan, or docetaxel as a second-line therapy in gastric or gastroesophageal junction adenocarcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 6-6 ◽  
Author(s):  
D. Cunningham ◽  
S. Park ◽  
Y. Kang ◽  
Y. Chao ◽  
L. Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Tumor Response ◽  
Phase Ii Study ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Randomized Phase Ii ◽  
Grade 3

6 Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan (CPT-11). In phase I studies, PEP02 has improved pharmacokinetics (PK) of CPT-11 and its active metabolite-SN38 with encouraging safety and tumor response in several cancer types including gastric cancer. This study evaluated the efficacy and safety of PEP02 (P), irinotecan (I) or docetaxel (D) as a single agent in gastric or gastroesophageal junction (GEJ) adenocarcinoma. Methods: A randomized, 3 arms (1:1:1), Simon's 2-stage (2/21, 5/41 based on tumor response) study was conducted in Europe and Asia. Patients (pts) with locally advanced or metastatic disease, failed to one prior chemotherapy, ECOG PS ≤ 2, at least 1 measurable lesion, no prior CPT-11 or taxane, were treated with P - 120 mg/m2, I - 300 mg/m2, or D - 75 mg/m2 every 3 weeks. PK and pharmacogenetics (PGx) samples were collected for pts in P and I arms. Results: A total of 135 pts were randomized with 132 (44 per arm) treated between Jan 2008 and Jun 2010. Pts demographics (P/I/D): median age: 56/62/58, male (%): 79.5/77.3/77.3, Pts from Europe (%): 54.6/52.3/56.8, metastatic (%): 97.7/90.9/97.7, gastric adenocarcinoma (%): 84.1/79.6/68.2, and ECOG 0 + 1 (%): 93.2/93.2/90.9. The confirmed responders of P/I/D were 6 (13.6%)/3 (6.8%)/7 (15.9%) and disease control were 27 (61.4%)/27 (61.4%)/24 (54.6%). These three arms have similar progression free survival and overall survival. If stratified by region, Asian pts had longer survival than European pts. Toxicities of P/I/D were: grade 3/4 neutropenia (%): 9.1/13.6/15.9. grade 3/4 diarrhea (%): 27.3/18.2/2.3, hand-foot syndromes (%): 0.0/6.8/18.2. It was notable that symptoms related to acute cholinergic syndrome were less reported in P arm than in I arm. The PK data showed the mean T1/2, Cmax and AUC0→∞ of SN-38 in P/I arms were 88.8/22.8 hr, 8.79/44.1 ng/mL and 879/440 hr x ng/mL. Conclusions: This randomized phase II study suggests that PEP02 improves the PK profile and tumor response over irinotecan, and it is as efficacious as docetaxel in the 2nd-line treatment for gastric or GEJ adenocarcinoma. PEP02 is worthy of further evaluation as either 1st- or 2nd-line setting in future gastric cancer studies. [Table: see text]

A randomized phase II study of continuous versus intermittent S-1 plus oxaliplatin in first-line treatment of patients with metastatic gastric carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4028-4028 ◽  
Author(s):  
Sook Ryun Park ◽  
Young-Iee Park ◽  
Jiyoung Rhee ◽  
Byung-Ho Nam ◽  
Sun-Young Kong ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Induction Treatment ◽  
Hematologic Toxicity ◽  
Randomized Phase Ii ◽  
Significant Difference ◽  
Grade 3 ◽  
Ecog Ps

4028 Background: We conducted a randomized phase II study to compare continuous vs. intermittent S-1 + oxaliplatin (SOX) after induction of 6 cycles of SOX in patients (pts) with metastatic gastric cancer (MGC). Methods: Pts >18 yrs with chemo-naive MGC, normal organ function, ECOG PS 0-2, and measurable or evaluable lesion(s) were initially given an induction treatment of 6 cycles of SOX (S-1 40 mg/m2 bid on D1-14 + oxaliplatin 130 mg/m2 on D1 q 3 wks). Pts with CR/PR or SD were randomized to continue SOX (arm A) until progression/intolerable toxicity or discontinue until progression when SOX was re-administered (arm B). The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), response rate, safety, quality of life, and biomarker correlative studies. Results: From July 2007 to Dec 2010, a total of 250 pts entered into the study. Median age was 53 yrs (range, 24-69); PS 0/1/2=13/219/18; M/F=162/88. Three pts did not receive treatment and 126 (50.4%) discontinued treatment before or at the completion of 6 cycles of SOX due to progression (45.6%), pt refusal (2.8%), or adverse events (2.0%). A total of 121 pts were randomized: 59 (48.8%) to arm A and 62 (51.2%) to arm B. Clinical characteristics were well balanced between arms. SOX continuation resulted in a significant reduction in the risk of progression (median PFS, 10.5 months for arm A vs. 7.2 months for arm B; HR=0.57, 95% CI 0.39-0.84, p=0.005). With a median follow-up of 34.0 months (range, 10.5-53.3 months), there was no significant difference in OS (median OS, 22.6 months for arm A vs. 22.7 months for arm B; HR, 0.79, 95% CI 0.51-1.25, p=0.31). Arm A had higher rates of grade 3/4 fatigue (28.8% vs. 8.1%, p=0.004) and neuropathy (25.4% vs. 8.1%, p=0.014) but other grade 3/4 hematologic (neutropenia, 35.6% vs. 32.3%; thrombocytopenia, 23.7% vs. 21.0%; anemia, 15.3% vs. 6.5%) or non-hematologic toxicity rates were not significantly different. Conclusions: Continuous chemotherapy with SOX after induction therapy improved PFS but not OS. Supported by NCC Grant 1010180 (S-1 and oxaliplatin was provided by JEIL Pharm. Co., Ltd. and sanofi-aventis Korea Co., Ltd., respectively).

Phase II Trial of 4′-Epi-Doxorubicin in Locally Advanced or Metastatic Gastric Cancer

1988 ◽  
Vol 74 (3) ◽  
pp. 313-315 ◽  
Author(s):  
Eduardo Cazap ◽  
Roberto Estevez ◽  
Mario Bruno ◽  
Daniel Levy ◽  
Carlos Algamiz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Metastatic Gastric Cancer ◽  
Phase Iii ◽  
Future Studies ◽  
Phase Iii Trials

Patients with locally advanced or metastatic gastric adenocarcinoma received an i.v. bolus of 4′-epi-doxorubicin, 75/mg/m2/cycle, every 21 days. Partial responses were observed in 5 of 23 evaluable patients (21.7%). Treatment was generally well tolerated and toxicity was mild. The response rate to epirubicin appears to be very similar to that reported for doxorubicin. Larger doses of epirubicin could be safely used in future studies, and further evaluation of epirubicin in phase III trials is indicated.

scholarly journals Preoperative or Perioperative Docetaxel, Oxaliplatin, and Capecitabine (GASTRODOC Regimen) in Patients with Locally-Advanced Resectable Gastric Cancer: A Randomized Phase-II Trial

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2790
Author(s):  
Manlio Monti ◽  
Paolo Morgagni ◽  
Oriana Nanni ◽  
Massimo Framarini ◽  
Luca Saragoni ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Free Survival ◽  
Peritoneal Lavage Cytology ◽  
Multicenter Phase ◽  
Randomized Phase Ii ◽  
Resectable Gastric Cancer ◽  
Lavage Cytology

Docetaxel associated with oxaliplatin and 5-fluorouracil (FLOT) has been reported as the best perioperative treatment for gastric cancer. However, there is still some debate about the most appropriate number and timing of chemotherapy cycles. In this randomized multicenter phase II study, patients with resectable gastric cancer were staged through laparoscopy and peritoneal lavage cytology, and randomly assigned (1:1) to either four cycles of neoadjuvant chemotherapy (arm A) or two preoperative + two postoperative cycles of docetaxel, oxaliplatin, and capecitabine (DOC) chemotherapy (arm B). The primary endpoint was to assess the percentage of patients receiving all the planned preoperative or perioperative chemotherapeutic cycles. Ninety-one patients were enrolled between September 2010 and August 2016. The treatment was well tolerated in both arms. Thirty-three (71.7%) and 24 (53.3%) patients completed the planned cycles in arms A and B, respectively (p = 0.066), reporting an odds ratio for early interruption of treatment of 0.45 (95% confidence interval (CI): 0.18–1.07). Resection was curative in 39 (88.6%) arm A patients and 35 (83.3%) arm B patients. Five-year progression-free survival (PFS) was 51.2% (95% CI: 34.2–65.8) in arm A and 40.3% (95% CI: 28.9–55.2) in arm B (p = 0.300). Five-year survival was 58.5% (95% CI: 41.3–72.2) and 53.9% (95% CI: 35.5–69.3) (p = 0.883) in arms A and B, respectively. The planned treatment was more frequently completed and was more active, albeit not significantly, in the neoadjuvant arm than in the perioperative group.

Phase I/II study of cetuximab, capecitabine and oxaliplatin (CAPOX) combined with standard radiotherapy (RTX) as neoadjuvant treatment of advanced rectal cancer (RC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3574-3574 ◽  
Author(s):  
D. Arnold ◽  
M. Hipp ◽  
T. Reese ◽  
W. Hohenberger ◽  
T. Liersch ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Egf Receptor ◽  
Neoadjuvant Treatment ◽  
Distant Metastases ◽  
Advanced Rectal Cancer ◽  
Phase Ii Trials ◽  
Standard Dosage ◽  
Chemotherapy Dose ◽  
Grade 3

3574 Background: CAPOX given concurrently to neoadjuvant RTX in RC is well tolerated and yielded high rates of pathologic complete responses in phase II trials. Cetuximab, a monoclonal antibody targeted against the EGF receptor, is active in metastatic colorectal cancer. Furthermore, synergy of cetuximab with RTX was shown in improved survival vs. RTX alone in head and neck cancer. This trial was to evaluate maximal tolerated dose (MTD), feasibility and efficacy of CAPOX + RTX with cetuximab in RC. Method: Patients (pts) had to have unpretreated T3–4 and/or N+ disease, with distant metastases allowed. During a conventionally fractionated RTX (1.8 Gy for 28 days [d]), cetuximab was given in standard dosage (400mg/m2 on d-7, then 6 weekly doses of 250 mg/m2, to d35). CAPOX was given on the basis of a previously examined schedule with oxaliplatin (50 mg/m2 d 1,8,22 and 29) in combination with capecitabine (d1–14 and d22–35) at 3 dose levels: 1000, 1300 and 1650mg/m2 bid. In phase I, a standard 3+3 design was used, allowing for dose escalation in 0/3 or 1/6 pt with dose-limiting toxicity (DLT). Results: 13 pts were enrolled: Median age 58 [35–75] yrs., m/f 7/6 pts. T3 85%, T4 15%; N+ 92%, M1 46%; G2 92%, G3 8%. As on dose level 1 one DLT (diarrhea grade 3) occurred, it was extended to 7 pts. No further DLT was observed as it was on levels 2 and 3 with 3 pts each. Full RTX course was administered in all pts, while CAPOX-cetuximab was stopped in the DLT case and cetuximab in 1 pt with hypersensitivity reaction. Toxicities are displayed in the table . Conclusion: CAPOX can safely be combined with cetuximab without requiring chemotherapy dose reduction. The multicenter phase II part of the trial with 31 pts. included so far is ongoing and updated results (including resectability) will be presented. [Table: see text] [Table: see text]

Phase II trial of irinotecan (Ir) plus cisplatin (CDDP) in patients with recurrent or metastatic squamous carcinoma of the head and neck (SCCHN)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6041-6041
Author(s):  
J. Gilbert ◽  
A. Cmelak ◽  
B. Burkey ◽  
R. Sinard ◽  
W. Yarborough ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Squamous Carcinoma ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Gi Toxicity ◽  
Prognosis Group ◽  
Ecog Ps ◽  
Dose Levels

6041 Background: Prognosis for recurrent or metastatic SCCHN patients remains poor with median survivals of 6–9 months. Therapies targeting this group are needed. We conducted a single arm Phase II trial of Ir plus CDDP in patients with recurrent or metastatic SCCHN. The goal of this trial was to evaluate the efficacy and toxicity of this combination in advanced SCCHN. Methods: Eligible patients had incurable SCCHN, an ECOG PS of 0–2 and were chemonaive (no prior chemotherapy or chemotherapy for primary disease at least 6 months prior to study entry). A two-stage accrual design (Simon) was used. Irinotecan 65 mg/m2 and CDDP 30 mg/m2 were administered weekly for 4 weeks, followed by a 2 week rest for a 6 week cycle. Due to GI toxicity and neutropenia, the Ir was decreased to 50 mg/m2 with CDDP 30 mg/m2. Response assessment was made after every cycle using WHO criteria. The primary endpoint was response rate. Results: Forty patients were enrolled (male: 33, female:7). Median age was 58 (33–79). Forty and 32 patients were evaluable for toxicity and response, respectively. Reasons for unevaluable: 7 without at least 1 full cycle of therapy; 1 patient with incomplete records. Overall response rate was 34% (11/32 PR) with 18% SD (6/32). Median progression free survival was 2.6 months. The median overall survival was 8.2 months. Toxicity was substantial at Ir 65 mg/m2 with a rate of Grade (G) 3 or 4 toxicity of 82% compared to 56% at Ir 50 mg/m2. For both dose levels, G 3 or 4 nausea and vomiting (23%), diarrhea (15%) and neutropenia (35%) were the most common toxicities. Conclusions: The combination of irinotecan and cisplatin is active in a poor prognosis group of patients. Toxicity of irinotecan at 65 mg/m2 with CDDP 30 mg/m2 is substantial. Irinotecan 50 mg/m2 and CDDP 30 mg/m2 is tolerable and provides a 34% response rate. No significant financial relationships to disclose.

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: A phase II study of the Belgian Group of Digestive Oncology.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 245-245 ◽  
Author(s):  
I. Borbath ◽  
A. Ceratti ◽  
C. Verslype ◽  
A. Demols ◽  
T. Delaunoit ◽  
...  
Keyword(s):  
Skin Rash ◽  
Phase Ii ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Standard Of Care ◽  
Egfr Expression ◽  
Prior Systemic Therapy ◽  
Ecog Ps

245 Background: Cholangiocarcinomas (CCK) are uncommon tumors with an increasing incidence and a poor prognosis. Epidermal growth factor receptor (EGFR) expression and activation in CCK have been demonstrated. Methods: We conducted a multicenter phase II trial combining cetuximab (Ctx), an anti-EGFR chimerized IgG1 monoclonal antibody, to gemcitabine (Gem). Patients with either locally advanced (LA) or metastatic (M) CCK (excluding gallbladder) were included; no prior systemic therapy was allowed. Ctx was administrated at the initial dose of 400 mg/m2 and further injections at 250 mg/m2 every 7 days, and Gem was administrated at 1000 mg/m2 on days 1, 8, and 15 every 4 weeks. The primary endpoint was the progression-free survival (PFS) rate at 6 months. A Simon 2-stage design was used. We hypothesized that Gem/Ctx would improve 6 month-PFS rate from 20% to 40%. We needed 3 patients with PFS ≥ 6 months from the first 13 to further include a total of 43 patients. Results: Forty-four patients with advanced CCK (41% LA/59%M) were enrolled from 09/2008 to 01/2010. Median age was 61.5 years (range 40-86) and baseline ECOG PS was 0 for 68% and 1 for 32% of the patients. Forty-three percent of the patients had prior surgery. Forty-six percent of the patients were free from progression at 6 months. Median PFS was 5.8 months (95% CI, 4.4-7.4 m) and median overall survival was 11.6 months (95% CI, 8.7-14.6 m). Nine patients (20.9%) had partial response with a median duration of 5 months (range 2-10 m). Disease control rate (PR + SD > 8 weeks) was 81.4%. The most common grades 3/4 related-toxicities were haematological abnormalities (47.7%), skin rash (13.6%) and fatigue (11.3%). Due to toxicity, 6 patients discontinued study treatment; 14 and 3 patients had a Gem and Ctx dose reduction respectively. Among the nine responders, 8 experienced a skin rash of at least grade 2, suggesting a relationship between skin toxicity and efficacy. Conclusions: Our study met its endpoint, i.e., a PFS rate of 46% at 6 months, suggesting that Gem-Ctx combination had promising activity with a manageable toxicity profile in advanced CCK. Adding Ctx to the new standard of care Gem-cisplatin deserves further investigations in CCK. [Table: see text]

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