Phase II study of panitumumab monotherapy in chemotherapy-naïve frail or elderly patients with unresectable, RAS wild-type colorectal cancer: OGSG 1602.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 106-106 ◽  
Author(s):  
Katsuya Ohta ◽  
Takeshi Kato ◽  
Masahiro Goto ◽  
Tetsuji Terazawa ◽  
Shingo Noura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Alternative Hypothesis ◽  
Performance Status ◽  
Single Agent ◽  
P Value ◽  
Intensive Chemotherapy ◽  
Wild Type ◽  
Grade 3

106 Background: Single agent of panitumumab (Pmab) is expected to be well tolerated and to improve survival in first-line setting in patients (pts) who are not eligible for intensive chemotherapy, although the efficacy and safety of Pmab for chemotherapy-naïve frail or elderly Japanese pts with wild-type (wt) RAS unresectable colorectal cancer (CRC) have not been yet studied. Methods: We conducted a multi-center phase II study. Pts aged over 76 years, or over 65 who were considered unsuitable for intensive chemotherapy. Pmab 6 mg/kg was administered intravenously every 2 weeks. The primary endpoint was disease control rate (DCR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and the incidence of grade 3 or 4 toxicities. Sample size was set to 36 with exact p-value of 0.05, a power of 0.90, the null of hypothesis of 45% and alternative hypothesis of 70% based on the Clopper-Pearson method. Results: A total 36 pts were enrolled in February 2017 to August 2018. Two pts were excluded; one was a lack of image examination at baseline, and the other was a lack of measurable lesion. The median age was 81 (67-88), with 29 pts (85%) being aged over 76 years. There were 33 (92%) pts with performance status (PS) 0/1, while two (6%) and one (3%) pts were PS 2/3, respectively. Twenty-eight pts (78%) had left-sided CRC, while eight pts had right-sided CRC. The RR was 50.0% (95%CI, 32.4-67.6) including three cases (8.8%) of complete response, and SD was 26.5%, yielding 76.5% of DCR (p < 0.001, 90% confidence interval [CI], 61.5-87.7). The RR with left sided tumor was 65% (95%CI, 44.3-82.8), while that pts with right-sided tumor was 0% (95%CI, 0.0-36.9)(p = 0.003). The major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 17%), hypomagnesemia (n = 4, 11%), fatigue (n = 3, 8%), paronychia (n = 3, 6%), and hyponatremia (n = 3, 6%). The grade 3 hematologic toxicities was neutropenia (n = 1, 3%). Conclusions: Pmab monotherapy showed the favolable efficacy and feasibility in the frail or elderly pts with RAS wt, unresectable CRC. The survival analysis including OS, PFS and TTF is awaiting. Clinical trial information: UMIN000024528.

scholarly journals First-line single-agent panitumumab in frail elderly patients with wild-type RAS unresectable colorectal cancer: a phase II study protocol OGSG 1602

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tetsuji Terazawa ◽  
Takeshi Kato ◽  
Masahiro Goto ◽  
Daisuke Sakai ◽  
Yukinori Kurokawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Phase Ii ◽  
Study Protocol ◽  
Frail Elderly ◽  
Phase Ii Study ◽  
Single Agent ◽  
Wild Type ◽  
First Line

Phase II study of bortezomib with cisplatin as first-line treatment of malignant pleural mesothelioma (MPM): EORTC 08052.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7081-7081 ◽  
Author(s):  
Mary O'Brien ◽  
Rabab Mohamed Gaafar ◽  
Sanjaykumar Popat ◽  
Francesco Grossi ◽  
Allan Price ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Dose Intensity ◽  
Line Treatment ◽  
First Line ◽  
Phase Ii Studies ◽  
Grade 3 ◽  
First Line Treatment

7081 Background: Cisplatin is one of the most active drugs available in MPM while bortezomib has shown some activity in single agent phase II studies against MPM. This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of MPM. Methods: Patients with histological proven MPM, with performance status (PS) 0/1, were eligible. The doses were cisplatin 75mg/m2 /3 wks and bortezomib 1.3mg/m2 day 1, 4, 8, 11 every 3 wks. The primary end-point was progression free survival rate at 18 wks (PFSR=18). The 2-stage Simon design (a=0.1; b = 0.05, P0=0.50 and P1=0.675) was used. In the first step of the study 37 eligible patients were planned. If more than 19 patients were alive and free of progression at 18 wks the total sample size was increased to 76 eligible patients. Results: Between 2007 and 2010 82 patients were entered. The median follow-up time is 32.3 months The median age was 55 years (range: 22-77yrs), male/female: 55/27 , PS 0/1: 9/73, Stage T1: 10%; T2: 42%, T3: 25%; T4: 23% and N0: 57%; N1: 4%; N2: 33%; N3: 6%. The median number of cycles received was 4 and 38% received 6 cycles. Cisplatin/ bortezomib dose intensity was 98/ 80%. Toxicity (grade 3/4): neutropenia 10%, thrombocytopenia 11%, anaemia 1%. Grade 3-4 hyponatraemia/ hypokalaemia occurred in 46/ and 17%. Grade 2 tinnitus, grade 3 fatigue occurred in 16%, and 12%, of patients. Motor/sensory/other neurotoxicity was grade 1: 6/28/7%, grade 2: 2/26/2% and grade 3: 1/7/2% respectively. There were 2 toxic deaths at 32 and 74 days due to acute pneumonitis and cardiac arrest. The PFRS-18 (including symptomatic progression) was 53% (80% confidence intervals, CI, 42-64%). The overall survival was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The PFS was 5.1 months (95% CI 3.3-6.5). Conclusions: On the basis of the PFRS-18, the null hypothesis could not be rejected, although CB gave predictable toxicity and was as active as other reported regimens in MPM.

Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma.

1993 ◽  
Vol 11 (9) ◽  
pp. 1737-1745 ◽  
Author(s):  
J L Grem ◽  
E Jordan ◽  
M E Robson ◽  
R A Binder ◽  
J M Hamilton ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Strong Association ◽  
Eastern Cooperative Oncology Group ◽  
Interferon Alfa ◽  
Hematologic Toxicity ◽  
Ifn Alpha ◽  
Grade 3

PURPOSE To test the activity of a regimen of interferon alfa-2a (IFN alpha-2a) 5 x 10(6) U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study. PATIENTS AND METHODS Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5-FU dose was increased by 15% if toxicity was mild, and decreased by 15% for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity. RESULTS Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54%; 95% confidence interval, 39% to 70%). A moderately strong association was noted between PS and response: PS O (n = 26), two CRs and 15 PRs (65%); PS 1 (n = 13), one CR and six PRs (54%); PS 2 (n = 5), zero CRs and zero PRs (0%; two-tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37%; diarrhea, 40%; rash, 7%; fatigue, 14%; granulocytopenia, 13%. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61%). Twelve patients (26%) required an IFN alpha-2a dose reduction for constitutional toxicity. CONCLUSION This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1.

Phase II Study of Capecitabine and Oxaliplatin in First- and Second-Line Treatment of Advanced or Metastatic Colorectal Cancer

2002 ◽  
Vol 20 (7) ◽  
pp. 1759-1766 ◽  
Author(s):  
Markus M. Borner ◽  
Daniel Dietrich ◽  
Roger Stupp ◽  
Rudolf Morant ◽  
Hanspeter Honegger ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
World Health ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Dose Reductions

PURPOSE: To determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the treatment of advanced nonpretreated and pretreated colorectal cancer. PATIENTS AND METHODS: Forty-three nonpretreated patients and 26 patients who had experienced one fluoropyrimidine-containing regimen for advanced colorectal cancer were treated with oxaliplatin 130 mg/m2 on day 1 and capecitabine 1,250 mg/m2 bid on days 1 to 14 every 3 weeks. Patients with good performance status (World Health Organization grade 0 to 1) were accrued onto two nonrandomized parallel arms of a phase II study. RESULTS: The objective response rate was 49% (95% confidence interval [CI], 33% to 65%) for nonpretreated and 15% (95% CI, 4% to 35%) for pretreated patients. The main toxicity of this combination was diarrhea, which occurred at grade 3 or 4 in 35% of the nonpretreated and 50% of the pretreated patients. Grade 3 or 4 sensory neuropathy, including laryngopharyngeal dysesthesia, occurred in 16% of patients on both cohorts. Capecitabine dose reductions were necessary in 26% of the nonpretreated and 45% of the pretreated patients in the second treatment cycle. The median overall survival was 17.1 months and 11.5 months, respectively. CONCLUSION: Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer. The main toxicity is diarrhea, which is manageable with appropriate dose reductions. On the basis of our toxicity experience, we recommend use of capecitabine in combination with oxaliplatin 130 mg/m2 at an initial dose of 1,250 mg/m2 bid in nonpretreated patients and at a dose of 1,000 mg/m2 bid in pretreated patients.

Oxaliplatin or Paclitaxel in Patients With Platinum-Pretreated Advanced Ovarian Cancer: A Randomized Phase II Study of the European Organization for Research and Treatment of Cancer Gynecology Group

2000 ◽  
Vol 18 (6) ◽  
pp. 1193-1202 ◽  
Author(s):  
Martine J. Piccart ◽  
John A. Green ◽  
Angel Jimenez Lacave ◽  
Nick Reed ◽  
Ignace Vergote ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Time To Progression ◽  
European Organization ◽  
Randomized Phase Ii ◽  
Grade 3

PURPOSE: This was a multicentric, open, randomized, phase II study of single-agent paclitaxel and oxaliplatin to evaluate the efficacy of oxaliplatin in a relapsing progressive ovarian cancer patient population and to analyze the safety profile and impact of both agents on quality of life, time to progression, and survival. PATIENTS AND METHODS: Eighty-six patients with platinum-pretreated advanced ovarian cancer were randomly assigned to two arms: 41 received paclitaxel at 175 mg/m2 over 3 hours every 3 weeks, and 45 received oxaliplatin at 130 mg/m2 over 2 hours every 3 weeks. For inclusion, patients had to have a performance status of 0 to 2 and to have received at least one and no more than two prior cisplatin- and/or carboplatin-containing chemotherapy regimens within the last 12 months. RESULTS: Seven confirmed responses were observed in each arm, for an overall response rate in the total treated population of 17% (95% confidence interval [CI], 7% to 32%) in the paclitaxel arm and 16% (95% CI, 7% to 29%) in the oxaliplatin arm. Median time to progression was 14 weeks and 12 weeks, and overall survival was 37 weeks and 42 weeks in the paclitaxel and oxaliplatin arms, respectively. Among 63 patients with a 0- to 6-month progression-free, platinum-free interval, there were five objective responses with paclitaxel in 31 patients and two objective responses with oxaliplatin in 32 patients. Nine patients (22%) in the paclitaxel arm had grade 3 or 4 neutropenia (National Cancer Institute of Canada [NCIC] Common Toxicity Criteria). Two patients (4%) experienced grade 3 thrombocytopenia in the oxaliplatin arm. Maximum grade (grade 3) NCIC neurosensory toxicity was experienced by three patients (7%) in the paclitaxel arm and by four patients (9%) in the oxaliplatin arm. CONCLUSION: Single-agent oxaliplatin at 130 mg/m2 every 3 weeks is active with moderate toxicity in patients with cisplatin-/carboplatin-pretreated advanced ovarian cancer.

Phase II study of combination therapy with S-1 and cetuximab in patients with KRAS wild-type unresectable colorectal cancer who had previously received irinotecan, oxaliplatin, and fluoropyrimidines (KSCC0901).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3558-3558
Author(s):  
Kazuma Kobayashi ◽  
Yasunori Emi ◽  
Yoshihiro Kakeji ◽  
Takao Takahashi ◽  
Eiji Oki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Combination Therapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Dihydropyrimidine Dehydrogenase ◽  
Treatment Protocol ◽  
Progression Free Survival ◽  
Wild Type ◽  
Open Label

3558 Background: Anti-epidermal growth factor receptor (anti-EGFR) antibodies alone or in combination with irinotecan (Iri) can be considered standard third-line therapy for KRAS wild-type (wKRAS) unresectable colorectal cancer (UNCRC). However, some UNCRC patients (pts) cannot tolerate Iri-containing therapy. S-1, an oral fluorouracil (FU) derivative, enhances the anti-tumor effect by inhibiting dihydropyrimidine dehydrogenase activity and reducing digestive toxicity. Combination therapy with cetuximab (C-mab) may restore 5-FU resistance in 5-FU–resistant CCs. Therefore, we examined the efficacy of S-1+C-mab therapy in wKRAS UNCRC pts, who had previously received Iri, oxaliplatin (OX), and FUs. Methods: The study design was multicenter, single-arm, open-label phase II study. The major inclusion criteria were written informed consent; histologically proven CRC and clinically proven UNCRC; presence of measurable lesions; previous therapy with Iri, OX, and 5-FU; documented progressive disease after 5-FU–based chemotherapy; wKRAS tumors; age ≥ 20 years; performance status (PS) 0–1; and adequate organ function. The treatment protocol was as follows: weekly durable intravenous (DIV) C-mab administration at 400 mg/m2 (day 1) and 250 mg/m2/week (except day 1) and oral administration of 80 mg/m2/day S-1 on days 1–28 of each 42-day cycle. The primary endpoint was progression-free survival (PFS). A sample size of 39 was planned for a threshold PFS of 3.5 months and expected value of 6.0 months, with one-sided alpha of 0.05 and beta of approximately 0.2. Results: One patient was ineligible; 38 pts (PS 0/1, 32/6; 1/2/>3 prior chemotherapy regimens, 4/23/11) were enrolled from 10/2009 to 12/2010. The median PFS (central review) was 5.5 months (90% CI: 4.4 – 5.7); median overall survival (OS), 13.1 months; and the best ORR, 36.8%. The most common grade 3–4 adverse events were neutrophils, hypokalemia, rash, and dry skin. Conclusions: This study showed that S-1+C-mab may be a promising and well-tolerated treatment choice of wKRAS UNCRC, who had previously heavily treated by Iri, OX and FUs.

Phase II study of first-line combined chemotherapy bevacizumab with modified RPMI regimen for elderly or frail patients with unresectable or metastatic colorectal cancer (OGSG0802) update analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14601-e14601
Author(s):  
Taroh Satoh ◽  
Takeshi Kato ◽  
Motoki Yoshida ◽  
Yasuhiro Miyake ◽  
Shigeyoshi Iwamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Combined Chemotherapy ◽  
First Line ◽  
Port Placement ◽  
Oral Agents ◽  
Grade 3

e14601 Background: The first-line combined chemotherapy RPMI regimen with bevacizumab (Bmab) in AVF2192g tri al were active. According to the results of efficacy and safety, a fluoropyrimidine (FU) + Bmab regimen is regarded as one of treatment options for 1st-line chemotherapy in many guidelines. We planned a phase II study of modified RPMI regimen with Bmab especially for elderly or frail Pts. Methods: Pts with confirmed unresectable/metastatic colorectal cancer without previous chemotherapy, and not suitable for intensive chemotherapy were enrolled. Pts received modified RPMI regimen (5-FU 600 mg/m2 and l-leucovorin 200 mg/m2 bolus day 1, 8, 15) and Bmab 5 mg/kg day 1, 15, q4w) until disease progression or study withdrawal. The primary endpoint was overall response rate (ORR), and the secondary endpoints were PFS, OS and safety. Results: 41 Pts were enrolled from 13 institutions. Pts characteristics were as follows; median age 76 (range 56-90); male/female, 18/23; ECOG performance status 0/1/2, 21/19/1. The ORR, the rate of best response, the disease control rate (CR+PR+SD) were 36.6%, 56.1%, 85.4%, respectively. Median follow-up period was 14.4 months(Updated results will be presented). 28 Pts (68%) had objective progression and a patient (2.4%) died without progression. The median PFS and OS were 9.0 months (95%CI, 7.5–19.6) and 24.0 months (95%CI, 20.1–NR). The incidences of grade 3 or 4 adverse events were: leukopenia (7%), neutropenia (24%), thrombocytopenia (2%), diarrhea (5%), anorexia (10%), fatigue (5%), stomatitis (7%) and hypertension (5%). Grade 3 febrile neutropenia and grade 4 pulmonary embolism was observed in one pt. Five pts (12%) discontinued the treatment due to severe or uncontrollable adverse event. Conclusions: The modified RPMI regimen with Bmab showed promising activity, and was well tolerated for elderly or frail Pts. ORR and the median PFS of this regimen were similar to historical data with FU + Bmab. This regimen may be a good option for patients with poor PS or elderly with advantages of not requiring percutaneous port placement nor compliance or oral agents. Clinical trial information: UMIN000002182.

Results of the Quad wild type arm of the AGITG ICECREAM study: A randomised phase II study of cetuximab alone or in combination with irinotecan in patients with refractory metastatic colorectal cancer with no mutations in KRAS, NRAS, BRAF or PIK3CA.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3572-3572 ◽  
Author(s):  
Jeremy David Shapiro ◽  
Subotheni Thavaneswaran ◽  
Craig Underhill ◽  
Kristy Pamela Robledo ◽  
Christos Stelios Karapetis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Wild Type ◽  
Response Characteristics ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps

3572 Background: Cetuximab (cet) increases survival in RAS wild-type (WT) metastatic colorectal cancer (mCRC) in first-line and chemorefractory patients (pts). Adding irinotecan (iri) to cet in refractory pts who had progressed on iri increased response and delayed progression in the BOND trial, which was conducted prior to recognition that RAS mutations are predictive of EGFR-inhibitor (EGFR-I) resistance. Subsequent trials in chemorefractory pts used single agent EGFR-I as standard. In the era of biomarker selection, the benefit of continuing iri versus single agent EGFR-I had not been resolved. Methods: ICECREAM is a randomised phase II trial evaluating cet v cet + iri in chemotherapy-refractory mCRC, stratified for KRAS G13D mutation (previously reported) or no mutations in KRAS, NRAS, BRAF and PI3KCA (Quad WT ). EGFR-I naïve, ECOG PS 0-1 pts, progressing within 6 months of iri and refractory (or intolerant) to fluoropyrimidine and oxaliplatin were randomised to cet 400mg/m2 IV loading then 250mg/m2 weekly +/- iri 180mg/m2q2 wks. The primary endpoint was progression-free survival at 6 months (6m PFS); secondary endpoints were response rate (RR), overall survival (OS), toxicity and quality of life (QOL). Results: From Nov 2012 to June 2016, 48 Quad WT pts were recruited: 2 ineligible (not iri-refractory, BRAF mutation) wre not included for analyses and a further 2 not evaluable for response. Characteristics were balanced between cet (n = 21) v cet-iri (n = 25), except for sex (male 62 v 72%) and primary site (left 95 v 68%). 6m PFS rate was 14% v 41%; HR 0.39 (95% CI: 0.20–0.78, p = 0.008). RR was 10% (2 PR) v 36% (1 CR, 8 PR); p = 0.04. Toxicities were higher with cet-iri; at least one grade 3/4 adverse event in 50 v 23%. No differences in global or specific QOL were seen. Conclusions: The AGITG ICECREAM trial confirms a significant synergy for the addition of iri to cet and improved PFS in Quad WT chemorefractory mCRC, echoing data in molecularly unselected pts. Clinical trial information: ACTRN12612000901808.

Phase II study of ganetespib, an hsp-90 inhibitor, in patients with refractory metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 467-467 ◽  
Author(s):  
Andrea Cercek ◽  
Jinru Shia ◽  
Marc Gollub ◽  
Pamela Joan Raasch ◽  
Ellen Hollywood ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Heat Shock Protein 90 ◽  
Treatment Interruption ◽  
Hsp90 Inhibitor ◽  
Grade 3 ◽  
Hsp 90

467 Background: To evaluate the safety and efficacy of ganetespib, a heat shock protein 90 (Hsp90) inhibitor, as monotherapy in patients with refractory metastatic colorectal cancer. Methods: A phase II study utilizing a two-stage design was performed in which patients received Ganetespib 200 mg/m2 intravenously (IV) one time per week for three weeks followed by a one week break. Patients underwent pre and 48 hour post treatment tumor biopsies. Immunohistochemistry (IHC) was performed for p/Erk, CyclinD1, p/Akt, HIF-1a, VEGFr2 , p70S6 and Hsp70. Archived and pre dose biopsy tissue was utilized for KRAS, BRAF and PIK3CA genotyping using a Sequenom platform. Results: Fifteen patients were treated (median age 58, range 44-79). There were no responders. Two patients had stable disease lasting 31 and 23 weeks. The most frequent grade 1/2 toxicities were diarrhea, fatigue, nausea/vomiting and elevated transaminases ( Table ). These complications did not result in any treatment interruption. The most frequent grade 3 adverse events were diarrhea (12%), fatigue (24%), and elevated AST(12%) and Alk phos(29%). Three (20%) patients required dose reductions, 1 grade 3 AST, 1 grade3 ALT and 1 grade 3 fatigue. Conclusions: This was the first study of an Hsp90 inhibitor in colorectal cancer. Ganetespib treatment did not produce tumor responses when administered as a single agent in refractory metastatic colorectal cancer with this dosing regimen. Overall the drug was well tolerated and the toxicity profile was minimal. Ganetespib may be used in combination in future studies. Correlative IHC analyses will be presented. [Table: see text]

Phase II trial of combined chemotherapy with S-1, oral leucovorin, and bevacizumab in heavily pretreated patients with metastatic colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 627-627
Author(s):  
Kazuhisa Yamaguchi ◽  
Hiroya Taniguchi ◽  
Azusa Komori ◽  
Yukiya Narita ◽  
Shiori Uegaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Severe Toxicity ◽  
Wild Type ◽  
Primary Resistance ◽  
Grade 3

627 Background: Regorafenib improves survival in refractory metastatic colorectal cancer (mCRC), but alternative chemotherapy is required to avoid severe toxicity. S-1+oral leucovorin (SL) has shown promising results in untreated mCRC without severe toxicity. TML trial demonstrated that continuation of bevacizumab (Bev) after progression prolongs overall survival. Thus, we hypothesized that combination chemotherapy of SL/Bev would be beneficial; we conducted a single-center phase II trial to assess the efficacy and safety of SL/Bev as a salvage therapy in mCRC. Methods: Major eligibility criteria were: mCRC with confirmed adenocarcinoma diagnosis; age > 20 years; ECOG performance status, 0–2; and progression after administration or intolerance to approved drugs for mCRC (5-FU, oxaliplatin, irinotecan, Bev, and anti-EGFR antibody, if KRAS wild-type). S-1 (80–120 mg/body) and leucovorin (25 mg) were orally administered for 1 week followed by 1 week rest. Bev (5 mg/kg) was administered on day 1 of every 2-week cycle. Primary endpoint was disease control rate (DCR). Results: Twenty-three patients were enrolled: 8 (35%) females; median age, 70 years (range, 38–78); and 14 (61%) with KRAS wild-type. DCR was 65% [95% confidence interval (CI), 41.3–82.7%] and response rate was 6% (95% CI, 1.1–27.0%). One patient experiencing partial response to SL/Bev had BRAF mutant tumor with primary resistance to XELOX+Bev as first-line and irinotecan+cetuximab as second-line chemotherapy. Median progression-free and overall survival period were 4.1 and 9.5 months, respectively. Major adverse events were mucositis, (grade 3, 12%), diarrhea (grade 3, 12%), and decreased hemoglobin (grade 3, 12%). Conclusions: SL/Bev was well tolerated and delayed progression; therefore, it can be an alternative chemotherapy for refractory mCRC. We will report the data from final analysis at the meeting. Clinical trial information: 000009083.

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