Oxaliplatin, irinotecan, bevacizumab followed by docetaxel, bevacizumab in inoperable gastric cancer: First efficacy results of a multicenter phase II trial (AGMT Gastric-3) of the Arbeitsgemeinschaft Medikamentöse Tumortherapie.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4074-4074
Author(s):  
Ewald Woell ◽  
Josef Thaler ◽  
Felix Keil ◽  
Wolfgang Eisterer ◽  
Michael A. Fridrik ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Objective Response ◽  
Chemotherapy Resistance ◽  
Phase Ii Trials ◽  
Medikamentöse Tumortherapie ◽  
Multiple Metastases ◽  
Grade 3 ◽  
Line Setting ◽  
Previous Phase

4074 Background: In our previous phase II trials (AGMT-Gastric-1 and AGMT Gastric-2) efficacy of oxaliplatin and irinotecan as well as oxaliplatin, irinotecan and cetuximab was shown. Time to progression however was short suggesting acquired chemotherapy resistance. Therefore sequential chemotherapy combined with bevacizumab is investigated in the presented trial. Methods: Oxaliplatin 85 mg/m2 biweekly (q2w) and irinotecan 125 mg/m2 q2w are administered for the first three months followed by docetaxel 50mg/m2 q2w for three months. Chemotherapy for 6 months is combined with bevacizumab 5 mg/kg q2w which is administered until progression. For this abstract 36 patients (pt.) with histologically proven unresectable and/or metastatic gastric adenocarcinoma have been evaluated in a first line setting. Median age: 62.5 years (range 26-80 years), PS 0: 25 patients, PS 1: 10 patients, missing: 1 patient, single metastatic site: 24 patients, multiple metastases: 10 patients, missing: 2. Results: Frequently reported adverse events (more than 20% of pt.) were predominantly grade 1 or 2 and included diarrhea (25/36, 69%), polyneuropathy (17/36, 47%), nausea (17/36, 47%), fatigue (15/36, 42%), neutropenia (13/36, 36%), abdominal pain (11/36, 31%), hypokalemia (9/36, 25%). Grade 3 and 4 toxicities included neutropenia (6/36, 17%), diarrhea (3/36, 8%), hypokalemia (3/36, 8%), anemia in (2/36, 6%), leucopenia (2/36, 6%), thrombocytopenia (1/36, 3%), nausea in (1/36, 3%). Objective response rate after 3 cycles was available in 25 patients: CR 1/25 (4%), PR 14/25 (56%), SD 8/25 (32%), PD 2/25 (8%). After 6 cycles there were 12 evaluable patients with CR 2/12 (16.7%), PR 5/12 (41.7%), SD 4/12 (33.3%) and PD 1/12 (8.3%). Conclusions: The combination of oxaliplatin and irinotecan with bevacizumab followed by docetaxel with bevacizumab is feasible and very active in advanced gastric cancer.

Oxaliplatin, irinotecan, bevacizumab followed by docetaxel, bevacizumab in inoperable gastric cancer: Final efficacy results of a multicenter phase II trial (AGMT Gastric-3) of the arbeitsgemeinschaft Medikamentöse tumortherapie (AGMT).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15041-e15041
Author(s):  
Ewald Woell ◽  
Felix Keil ◽  
Josef Thaler ◽  
Birgit Gruenberger ◽  
Michael Hejna ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Maintenance Therapy ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Progression Rate ◽  
Medikamentöse Tumortherapie ◽  
Multiple Metastases ◽  
Grade 3 ◽  
Line Setting

e15041 Background: We could show efficacy of oxaliplatin and irinotecan as well as oxaliplatin, irinotecan and cetuximab in previous trials.Time to progression however was short suggesting acquired chemotherapy resistance.To address this problem sequential chemotherapy combined with bevacizumab is investigated in the presented Gastric-3 trial. Methods: Oxaliplatin 85 mg/m2 and irinotecan 125 mg/m2 are administered biweekly (q2w) for the first three months followed by docetaxel 50mg/m2 q2w for subsequent three months. Chemotherapy is combined with bevacizumab 5 mg/kg q2w which is administered until progression. Primary endpoint is response rate. 40 patients (pts.) with histological proven unresectable and/or metastatic gastric adenocarcinoma treated in a first-line setting are evaluated. Median age: 62.5 years PS 0: 26 pts., PS 1: 12 pts., missing: 2 pts.,single metastatic site: 25 pts., multiple metastases: 13 pts., missing: 2. Results: Frequently reported adverse events (more than 20% of pts.) were predominantly grade 1 or 2 and included diarrhea (72.5%), nausea (65%), emesis (50%), abdominal pain (50%), fatigue (47.5%), polyneuropathy (40%), neutropenia (25%), hypokalemia (22.5%), hypertension (22.5%). Grade 3 and 4 toxicities included neutropenia (25%), diarrhea (12.5%), ileus/subileus (10%), hypokalemia (7.5%), leucopenia (7.5%), anemia (5%), meningiosis carcinomatosa (5%). Objective response rate after 3 cycles was available in 31 patients: CR 1/31 (3.2%), PR 48.4%, SD 35.5%, PD 12.9%. After 6 cycles there were 14 evaluable patients with CR 2/14 (14.3%), PR 42.9%, SD 35.7% and PD 7.1%. Median progression free survival was 32 weeks, median overall survival was53 weeks. Progression rate or death was 34/40 (85%), mortality 29/40 (72.5%). Maintenance therapy was given in 12/40 pts. (30%). Median time on maintenance therapy was 17 weeks, range (2 – 77). Conclusions: The combination of oxaliplatin and irinotecan with bevacizumab followed by docetaxel with bevacizumab is feasible and active in advanced gastric cancer. Clinical trial information: 2008-006128-79.

Oxaliplatin, irinotecan, and cetuximab in advanced gastric cancer. First efficacy results of a multicenter phase II trial (AGMT Gastric-2) of the Arbeitsgemeinschaft Medikamentoese Tumortherapie (AGMT)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4538-4538
Author(s):  
E. Woell ◽  
R. Greil ◽  
W. Eisterer ◽  
M. Fridrik ◽  
B. Grünberger ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Multicenter Phase ◽  
Grade 3 ◽  
Line Setting

4538 Background: Patients (pts.) suffering from advanced gastric cancer have still a poor prognosis and treatment options are limited. In our previous phase II trial (AGMT-Gastric-1) we could show that the combination of oxaliplatin and irinotecan was well tolerated and showed an objective response rate of 58% (Anticancer Res 28:2901–2906, 2008). This chemotherapy regimen was tested in combination with cetuximab in a multicenter phase II trial. Methods: Oxaliplatin 85 mg/m2 biweekly and irinotecan 125 mg/m2 biweekly were combined with cetuximab 400 mg/m2 loading dose and subsequently weekly 250 mg/m2. 51 patients with histological proven unresectable and/or metastatic gastric adenocarcinoma were treated in a first line setting. Median age: 62 years (range 19–79 years), PS 0: 25 patients, PS 1+2 26 patients, single metastatic site: 24 patients, multiple metastases: 27 patients. Results: Frequently reported adverse events (more than 20% of pts.) were predominantly grade 1 or 2 and included neutropenia (35% of pts.), thrombocytopenia (33%), anemia (73%), nausea (45%), diarrhea (57%), alopecia (22%), and fatigue (37%). Grade 3 and 4 toxicities included neutropenia in 9/1 pts., thrombocytopenia in 1/0 pts., anemia in 3/1 pts., nausea in 2/0 pts., and diarrhea in 7/2 pts. Sensory neuropathy occurred mostly as grade 1 and 2 in 37% of pts., in 7 pts. grade 3 neurotoxicity was observed. Acneiform skin rash grade 1 / 2 / 3 / 4 was reported in 31% / 20% / 6% / 2% of pts. respectively. 16 pts. went off-study due to neutropenia (n=5), nausea/vomiting (n=1), diarrhea (n=1), progressive disease (n=3), toxic colon (n=2), and allergic reaction to cetuximab at first (n=2), second (n=1) or third infusion (n=1). 35 patients are assessable for response with 1 pt. (3%) showing a CR, 21 pts. (60%) a PR, 7 pts. (20%) a SD and PD in 6 pts. (17%). A disease control rate was achieved in 83%. Median time to progression was 24.8 weeks (n=29), median overall survival 38.1 weeks (n=32). Conclusions: The combination of oxaliplatin and irinotecan with cetuximab is feasible, safe and active in advanced gastric cancer. [Table: see text]

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]

Phase II study of paclitaxel, cisplatin, and 5-FU combination chemotherapy in patients with advanced gastric cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15052-15052
Author(s):  
S. Cho ◽  
H. Shim ◽  
S. Lee ◽  
J. Ahn ◽  
D. Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bone Marrow ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Study ◽  
Objective Response ◽  
Dose Intensity ◽  
Bone Marrow Suppression ◽  
Grade 3

15052 Background: Taxane has been used widely in advanced gastric cancer, but toxicities are problematic. To avoid the bone marrow suppression, docetaxel could be replaced paclitaxel to reduce bone marrow suppression and to improve the efficacy, we planned to augmentation of the dose intensity. This phase II study evaluated the efficacy and safety of combination chemotherapy with paclitaxel, cisplatin, and 5-fluorouracil (5-FU) in advanced gastric cancer. Methods: Patients with histologically confirmed gastric adenocarcinoma, ECOG PS = 2, at least one measurable lesion and adequate organ functions were eligible. Paclitaxel (175 mg/m2) and cisplatin (75 mg/m2) were given as a 1-h intravenous infusion on day 1, followed by 5-FU (750 mg/m2) as a 24-h continuous infusion for 5 days. This cycle was repeated every 3 weeks. Results: Forty-five eligible patients (median age 56 years) were treated in this way. Of the 41 patients in whom efficacy was evaluable, an objective response rate (ORR) was seen in 20 (48.8%), a complete response in two, and a partial response in 18 patients. The median time to progression was 6.9 months (95% CI, 5.86–7.94), and the median overall survival was 13.1 months (95% CI, 8.83–17.37). The main hematological toxicity was neutropenia and greater than grade 3 neutropenia was observed in 67 cycles (25%). Febrile neutropenia developed in three patients (7.3%). The major non-hematological toxicities were asthenia and peripheral neuropathy, but grade 3 or 4 toxicity was not seen. Conclusions: The combination chemotherapy with paclitaxel, cisplatin, and 5-FU is a promising regimen, and was well tolerated in patients with advanced gastric cancer. No significant financial relationships to disclose.

A phase II study of irinotecan, oxaliplatin, 5-fluorouracil, leucovorin (FOLFOXIRI) as a first-line chemotherapy in metastatic gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4076-4076
Author(s):  
J. Lee ◽  
W. Kang ◽  
S. Lee ◽  
J. Kwon ◽  
H. Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Gastric Cancer ◽  
Efficacy And Safety ◽  
First Line ◽  
Grade 3

4076 Background: Previous phase II study showed a high efficacy and safety of FOLFOXIRI (irinotecan, oxaliplatin, 5-fluorouracil, leucovorin) combination chemotherapy in metastatic colorectal cancer. This non-randomized open label phase II study evaluated the efficacy and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients. Methods: Patients with: histologically proven, bidimensionally measurable, metastatic gastric adenocarcinoma, age 18 - 70 years, with a performance status 0 - 2, no prior chemotherapy or at least 12 months after adjuvant therapy, life expectancy > 3 months, signed written informed consent were eligible. Treatment consisted of irinotecan 150 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 100 mg/m2 day and 5-fluorouracil 2000 mg/m2 as a 48-h continuous infusion starting on day 1, repeated every 2 weeks until unacceptable toxicity, patients’ refusal, or up to 12 cycles. The planned sample size was 48 and the primary endpoint was response rate. Results: From August 2004 to August 2005, 48 patients were prospectively enrolled. The median age was 54 years (24 - 69) and male:female ratio was 1.3:1. In total, 379 cycles were administered with a median of 9 cycles per patient (range, 1–12) and 45/48 patients were evaluable for treatment response. Three patients were not assessable for response due patients’ refusal for further chemotherapy following the first cycle. By per-protocol analysis, the objective response rate was 73.3 % (95% CI, 60.8–85.8) with 2 CRs and 31 PRs. Four patients (9%) had stable disease and 8 patients (18%) had progressive disease. The estimated median survival of all patients was 14.0 months (95% CI, 11.8 - 16.2 ) and the estimated median time-to-progression was 8.9 months (95% CI, 6.7–11.0). In total of 379 cycles administered, most common grade 3/4 toxicities were neutropenia (11% of all cycles) and emesis (12%). Grade 2 peripheral neuropathy occurred in 5 patients. One (2%) patient had severe tumor bleeding and 5 (10%) patients experienced grade 3 diarrhea. Conclusions: FOLFOXIRI combination chemotherapy showed a very promising preliminary anti-tumor activity and was generally well tolerated as a first-line treatment for patients with metastatic gastric cancer. No significant financial relationships to disclose.

A randomized phase II study of a combination of docetaxel and S-1 versus docetaxel monotherapy in pts with NSCLC previously treated with platinum-based chemotherapy: Results of Okayama Lung Cancer Study Group (OLCSG) trial 0503

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8058-8058
Author(s):  
Y. Segawa ◽  
K. Hotta ◽  
N. Takigawa ◽  
K. Matsuo ◽  
H. Yoshioka ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Median Number ◽  
Lung Cancer Study Group ◽  
Randomized Phase Ii ◽  
Platinum Based Chemotherapy ◽  
Grade 3 ◽  
Line Setting ◽  
Ecog Ps

8058 Background: Recent studies have demonstrated that docetaxel (DOC) monotherapy provides a significant survival prolongation in relapsed pts with NSCLC. However, its benefit remains modest and further improvement is needed. S-1 is a newly developed oral 5-fluorouracil derivative, possessing a promising anti-tumor activity in NSCLC. Based on a superior effect of combination of DOC and 5-fluorouracil derivative (capecitabine) to DOC alone in anthracycline-pretreated breast cancer pts, we conducted a randomized phase II study to evaluate the clinical significance of adding S-1 to DOC in the second-line setting. Methods: Pts with relapsed NSCLC to the first-line platinum-based chemotherapy were randomly allocated to DOC monotherapy (A arm; 60 mg/m2, day 1, q 3 wks) or a combination chemotherapy (B arm) of DOC (40 mg/m2, day 1, q 3 wks) and S-1 (80 mg/m2, days 1 to 15). The doses of arm B were determined based on the results of a phase I study conducted for Japanese pts with gastric cancer (Anticancer Res 24: 1843, 2004). The primary endpoint was response rate and secondary endpoints included OS, PFS and toxicity. Results: Between 2005 and 2008, 60 pts were enrolled (A/B: 29/31 pts). Demographics of the pts were as follows: M/F: 49/11, Ad/others: 40/20, ECOG-PS 0/1: 38/22. A median number of courses administered was 4 (range: 1 to 6). Objective response was obtained in 6 (20.7%) and 5 pts (16.1%) in arms A and B, respectively. With a median follow-up time of 16.9 months, MST and median PFST in arm A were longer than arm B (22.9 vs. 8.7 months and 3.7 vs. 3.4 months, respectively). The major toxicity was myelosuppression, with grade 4 neutropenia of 62% vs. 29%, whereas thrombocytopenia was generally mild. Grade 3 febrile neutropenia was observed in 4 and 1 pts, none of whom further developed grade 5 toxicity. Other grade 3 or greater non-hematological adverse events included fever (B: 1 pt), pneumonitis (B: 1 pt), liver dysfunction (B: 2 pts), skin rash (B: 1 pt), and all of them were improved with an appropriate supportive care. Conclusions: The trial suggests that docetaxel monotherapy remains a standard therapy for NSCLC pts who relapsed to platinum-based chemotherapy. No significant financial relationships to disclose.

Sunitinib as second-line treatment for advanced gastric cancer: preliminary results from a phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4603-4603 ◽  
Author(s):  
Y. Bang ◽  
Y. Kang ◽  
W. Kang ◽  
N. Boku ◽  
H. Chung ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Mucosal Inflammation ◽  
Open Label ◽  
Preliminary Results ◽  
Grade 3

4603 Background: Sunitinib malate (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, and FLT3, approved internationally for the treatment of advanced RCC and imatinib-resistant or -intolerant GIST. We investigated the safety and activity of SU monotherapy in pts with previously-treated gastric cancer. Preliminary results from this open-label, multicenter, phase II study are reported. Methods: Eligibility criteria included measurable stage IV disease; 1 prior chemotherapy regimen; and ECOG PS =1. Pts took SU 50 mg/day for 4 wks followed by 2 wks off treatment in 6-wk cycles. A Simon 2-stage design was used with a target accrual of 38 pts in the first stage, expanding to 63 pts if =2 partial responses (PRs) were observed. The primary endpoint was RECIST-defined objective response rate. Secondary endpoints included duration of response and safety. Pharmacokinetic (PK) Ctrough parameters were also monitored. Results: As of Sept 15 2006, 38 evaluable pts (median age 56 years [range 29–78]; 2–3 metastatic sites [63%]; prior treatment with 5-FU ± platinum [P] [24%], capecitabine ± P [13%], TS-1 ± P [26%], other [37%]) have received a median of 2 SU cycles (range 1–3). Of 21 pts evaluable for efficacy, 1 PR has been confirmed and 8 pts had stable disease (SD), 4 with SD for =2 cycles. The most commonly reported AEs were typically grade 1/2 in severity and included stomatitis, skin discoloration, fatigue, anorexia, diarrhea, hand-foot syndrome (HFS), nausea and vomiting. Grade 3/4 toxicities included HFS (10.5%), fatigue (7.9%), anorexia (7.9%) and mucosal inflammation (5.3%). Grade 3/4 hematologic toxicities included neutropenia (29%), thrombocytopenia (29%) and anemia (11%). 7 pts experienced serious SU- related AEs requiring dose modifications in 3 pts and treatment discontinuation in 1 pt. Preliminary PK investigations indicate that concentrations seen in gastric pts are similar to those seen in other pts treated with SU. Conclusions: These initial findings show that SU is generally well tolerated and may have single-agent antitumor activity in pre-treated gastric cancer pts. Further trials with SU in combination with standard chemotherapy regimens are planned. No significant financial relationships to disclose.

ABI-007 in the treatment of unresectable or recurrent gastric cancer refractory to fluoropyrimidine-containing regimen: Updated data from the multicenter phase II study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 90-90 ◽  
Author(s):  
Hiroya Takiuchi ◽  
Yasutsuna Sasaki ◽  
Tomohiro Nishina ◽  
Hirofumi Yasui ◽  
Kei Muro ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Recurrent Gastric Cancer ◽  
Infusion Schedule ◽  
Grade 3 ◽  
Gastric Cancer Patients

90 Background: ABI-007 is a novel Cremophor-free nanoparticle albumin-bound paclitaxel. Cremophor-free formulation allows administration using a shorter infusion schedule (30 minutes) and without the need for premedicaion to prevent solvent-based hypersensitivity reactions.This single arm phase II study evaluated the efficacy and safety of ABI-007 given every three weeks to unresectable or recurrent gastric cancer patients (pts) who had received one prior chemotherapy regimen containing fluoropyrimidine and developed disease progression (PD) or recurrence. Methods: Eligibility include: histologically or cytologically confirmed gastric adenocarcinoma , received one prior regimen containing fluoropyrimidine analogs and developed PD or recurrence, age: 20 - 74, at least one measurable lesion by RECIST(1.0), PS:0-2, adequate organ function and written informed consent. Study duration was until PD or unacceptable toxicity developed. Pts received ABI-007 260 mg/m2, i.v. on day 1 of each 21 day cycle) without premedication. The primary endpoint was overall objective response rate (ORR). Results: From April 2008 to July 2010, total of 56 pts were enrolled, 55 received the study treatment, and 54 pts were evaluable for response. Median age was 64, Male/Female was 43/12, PS:0/1/2 was 33/22/0 and number of sites of metastasis corresponding was 1/2/≥3:19/21/15. ORR was 27.8% (15/54; 95%CI, 16.5-41.6) and DCR (disease control rate:CR+PR+SD) was 59.3% (32/54, 95%CI, 45.0-72.4) for all evaluable patients. One confirmed CR was observed. Median progression–free survival was 2.9 months (95%CI, 2.4-3.6), and median overall survival was 9.0 months (95%CI, 6.6-11.5). The most common grade 3/4 toxicities were neutropenia (49.1%), leucopenia (20.0%), lymphopenia (10.9%); and peripheral sensory neuropathy (23.6%). Conclusions: These data demonstrate that ABI-007 showed promising activity with well-tolerated toxicities for previously treated unresectable or recurrent gastric cancer pts.

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

795 A multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A843-A843
Author(s):  
Michael Wagner ◽  
Megan Othus ◽  
Sandip Patel ◽  
Christopher Ryan ◽  
Ashish Sangal ◽  
...  
Keyword(s):  
Phase Ii ◽  
Immune Checkpoint ◽  
Uv Light ◽  
Light Exposure ◽  
Case Reports ◽  
Objective Response ◽  
Open Label ◽  
Primary Tumors ◽  
Multicenter Phase ◽  
Grade 3

BackgroundAngiosarcoma is a rare cancer of endothelial cells that can be aggressive and carries a high mortality. A subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and UV light exposure DNA mutational signature. Isolated case reports have suggested clinical efficacy of immune checkpoint blockade in angiosarcoma; no prospective studies of immune checkpoint inhibition in angiosarcoma have been reported. We report efficacy analysis results for patients with advanced or unresectable angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing phase II study for rare cancers (NCT02834013).MethodsThis is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1mg/kg IV q6weeks) plus nivolumab (240mg IV q2weeks) for patients with metastatic or unresectable angiosarcoma. Primary endpoint is objective response rate as assessed by RECIST v1.1, including measurable cutaneous disease that can be followed by photography. Secondary endpoints include PFS, OS, stable disease at six months, and toxicity. A two-stage design is used with six patients in the first stage and an additional ten patients in the second stage.ResultsAt data cutoff, 16 patients with angiosarcoma were enrolled. Median age was 68 years (25-81 years). Median number of prior lines of therapy was 2 (0-5). 9 patients had cutaneous primary tumors of any cutaneous site, 7 had non-cutaneous primary tumors. ORR for all patients was 25% (4/16, table 1, figure 1). Subgroup analysis revealed that 60% (3/5) of patients with primary cutaneous tumors of the scalp or face had a confirmed objective response. 6-month PFS was 38%. 75% of patients experienced an adverse event (AE), and 25% experienced a grade 3-4 AE. 68.8% experienced an immune related AE (irAE), and 2 (12.5%) developed grade 3 or 4 irAEs. Grade 3-4 irAEs were ALT and AST increase and diarrhea. There were no grade 5 toxicities.ConclusionsThe combination of ipilimumab and nivolumab was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site, with 3 of 5 patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma.AcknowledgementsFunding: National Institutes of Health/National Cancer Institute grant awards CA180888, CA180819, CA180868; and in part by Bristol-Myers Squibb CompanyTrial RegistrationNCT02834013Ethics ApprovalThis study was approved by the NCI CIRB.

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