A multicenter phase II trial of mFOLFOX6 plus bevacizumab as treatment for liver-only metastases from colorectal cancer unsuitable for upfront resection (TRICC 0808).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 543-543
Author(s):  
Hiroyuki Uetake ◽  
Masamichi Yasuno ◽  
Megumi Ishiguro ◽  
Shingo Kameoka ◽  
Yasuhiro Shimada ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Resection ◽  
Phase Ii ◽  
Conversion Rate ◽  
Phase Ii Trial ◽  
Liver Tumors ◽  
R0 Resection ◽  
Serum Total Bilirubin ◽  
Resection Rate ◽  
Grade 3

543 Background: Liver resection is a standard treatment for resectable liver metastases (mets) from colorectal cancer. In patients (pts) with multiple or large liver mets, liver tumors may not be resected completely or recurrence after complete resection are frequently observed. Methods: This prospective single arm phase II trial assessed R0 liver resection rate after mFOLFOX6 + bevacizumab (BV) in pts with liver mets considered unsuitable for upfront resection. Pts with liver-only mets, those were larger than 5cm in diameter or more than 4 in number, were treated with 6 cycles of mFOLFOX6 + BV (without BV in the 6th cycle). After chemotherapy, resectability of liver mets was assessed by CT or MRI. Secondary endpoints included liver resection rate, conversion rate from unresectable to resectable, safety of liver resection, recurrence rate, and survival. Results: Between May 2009 to October 2011, 46 pts were registered (one was excluded after registration due to ineligibility). Among the 19 pts with resectable mets at entry, 18, except one who refused the continuation of chemotherapy after the first cycle, underwent liver resection after 6 cycles of chemotherapy. In 16 of the 18 pts, R0 resection was performed. Among the 26 pts with unresectable mets at entry, 6 underwent liver resection and 4 had R0 resection. Overall R0 resection rate, liver resection rate and conversion rate were 44.4% (20/45), 53.3% (24/45) and 23.1% (6/26), respectively. The grade 3/4 adverse effects (AEs) by mFOLFOX6 + BV included fatigue (6.5%), stomatitis and nausea (2.2%), neutropenia (16.3%) and increase of serum total bilirubin (2.2%). As to BV related grade 3/4 AEs, hypertension (6.5%) and thromboembolism (2.2%) were observed. After liver resection, grade 3 wound infection, intra-abdominal abscess and delayed wound healing were complicated in two, in one and in one, respectively. Conclusions: In pts considered unsuitable for upfront resection of liver-only mets, mFOLFOX6 + BV was associated with high R0 resection rate, liver resection rate and conversion rate without severe toxicities and surgical complications. Updated results including survival will be presented. Clinical trial information: UMIN000002101.

A multicenter phase II trial of mFOLFOX6 plus bevacizumab as treatment for liver-only metastases from colorectal cancer unsuitable for upfront resection (TRICC0808): Final analysis for survival.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 704-704
Author(s):  
Hiroshi Tamagawa ◽  
Hiroyuki Uetake ◽  
Megumi Ishiguro ◽  
Nobuyuki Mizunuma ◽  
Yusuke Kinugasa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Resection ◽  
Liver Metastasis ◽  
Recurrence Rate ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Large Population ◽  
Final Analysis ◽  
R0 Resection ◽  
Resection Rate

704 Background: TRICC0808 trial is a phase II trial to evaluate the liver resection rate and safety after mFOLFOX6 + bevacizumab therapy for liver-only metastasis that is unsuitable for upfront resection (H2 and H3) from colorectal cancer. Primary endpoint was the R0 resection rate, which was reported to be 44.4% (Ann Surg Oncol 22: 908-915, 2015). Final analysis of TRICC0808 was performed (February 16, 2015 data fixation). Methods: Forty six patients were registered and OS was analyzed for 45 patients (FAS). In 24 cases with liver resection after protocol chemotherapy, RFS, recurrence rate and recurrence patterns were analyzed. Results: The1, 2 and 3 year OS rate in FAS from the starting date of the chemotherapy was 91.1%, 68.9%, 44.0%, respectively, with 2.80 years of MST. The 3 year OS rate in 31 patients with liver resection including resection after additional chemotherapy was 61.3% with 3.59 years of MST, which was better than 0% of the 3 year OS rate with 1.75 years of MST in patients without liver resection. In 24 who underwent liver resection after 6 cycles of protocol chemotherapy, the 1, 2 and 3 year RFS rate was 29.2%, 12.5%, 8.3%, respectively, with 3.07 years of MST. The recurrence rate for 20 patients with R0 liver resection was 80%, and 100% in those with R1 and R2 liver resection. In the 20 patients with R0 liver resection, the 3 year OS rate of 16 patients with technically resectable liver metastasis at registration and 4 with technically unresectable tumors was 53.6% and 50.0%, respectively. Conclusions: The present final analysis of TRICC0808 trial disclosed good OS in the patients with liver resection, though the large population of the patients recurred afterward. The results were concordant with those of other reported trials for liver metastasis which is unsuitable for upfront resection. Liver resection was thought to be effective for liver metastasis which converted from unresectable to resectable after chemotherapy. Clinical trial information: UMIN000010209.

Multicenter phase Ib/II study of everolimus (RAD001) and tivozanib (AV-951) in patients with refractory, metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
Brian M. Wolpin ◽  
Kimmie Ng ◽  
Andrew X. Zhu ◽  
Thomas Adam Abrams ◽  
Peter C. Enzinger ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Once Daily ◽  
Phase Ib ◽  
Multicenter Phase ◽  
Grade 3 ◽  
Ecog Ps

560 Background: Everolimus (E) is an oral inhibitor of mTOR. Tivozanib (T) is a highly potent, selective, oral inhibitor of VEGF receptors-1, -2, and -3. Preclinical data suggest antitumor activity for this combination in colorectal cancer. We therefore performed a multicenter Phase Ib trial of E + T in patients (pts) with any refractory gastrointestinal (GI) malignancy, followed by a Phase II trial of E + T in pts with refractory, metastatic colorectal cancer (mCRC). Methods: Eligibility criteria: histologically confirmed, measurable disease; ECOG PS≤2; blood pressure ≤150/100; no venous thromboembolism within prior 6 months. Pts with mCRC must have received prior fluoropyrimidine, irinotecan, oxaliplatin, bevacizumab and anti-EGFR antibody (if KRAS wt). E was administered once daily continuously. T was administered once daily for 3 out of every 4 weeks. The Phase Ib study in pts with any GI malignancy followed a standard 3+3 design with 3 dose levels: (1) E 5 mg/d + T 1 mg/d; (2) E 10 mg/d + T 1 mg/d; (3) E 10 mg/d + T 1.5 mg/d. The Phase II study in pts with mCRC was a non-randomized, one-stage design with a primary endpoint of progression-free survival. Results: Between 02/10-12/10, 12 pts were enrolled to the Phase Ib study. Median age, 60 (39-81) years; male, 50%; ECOG PS 0/1/2, 42/58/0%; tumor types: esophagus 1, colorectal 11 pts. Dose limiting toxicities of grade 3 fatigue and grade 3 fatigue/ dehydration occurred in 2/6 pts on dose level 3. Grade 3/4 treatment-related adverse events in ≥10% of pts were dehydration, fatigue, headache, hyperglycemia, hypertension, and hypophosphatemia. The phase II study proceeded at the maximally tolerated dose (MTD) of E 10 mg/d and T 1 mg/d. Between 02/11-06/11, 40 pts with mCRC were enrolled to the phase II study. All but 1 pt received prior bevacizumab. Median age, 56 (35-81) years; male, 48%; ECOG PS 0/1/2, 45/53/2%. Treatment is ongoing. Conclusions: Among pts with refractory GI malignancies, the combination of Everolimus + Tivozanib was well-tolerated with MTD of E 10 mg/d and T 1 mg/d. A phase II trial has completed enrollment using these doses of E + T in pts with refractory mCRC; safety and efficacy data will be available for presentation.

Phase II trial of modified FOLIRI plus Panitumumab as first-line treatment in elderly patients with RAS wild-type metastatic colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15053-e15053
Author(s):  
Athanasios Karampeazis ◽  
Lampros Vamvakas ◽  
Nikolaos K. Kentepozidis ◽  
Athanasios Kotsakis ◽  
Kostas Kalbakis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Line Treatment ◽  
Wild Type ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

e15053 Background:The role of combination chemotherapy plus anti-EGFR treatment in older patients with metastatic colorectal cancer (mCRC) is unclear. We conducted an open label phase II trial in order to evaluate the safety and efficacy of modified FOLFIRI plus panitumumab as first-line treatment in elderly patients with RAS wild-type mCRC. Methods: Patients ≥70 years old with unresectable all-RAS wild-type mCRC were treated with Panitumumab 6mg/kg as 60min iv infusion followed by Irinotecan 130mg/m2 as 90min iv infusion, Leucovorin 400mg/m2 as 2h iv infusion and 5-Fluorouracil 400mg/m2 as bolus iv infusion on day 1 and 5-Fluorouracil 1.200 mg/m2 as continuous iv infusion for 46h, every 2 weeks. Sample size calculation was based on the minimax Simon two-step design: The null hypothesis was that the overall response rate (ORR) is ≤ 30% versus the alternative hypothesis of ORR ≥ 50% (α = 0.05, power 80%). Results: Forty-six patients were enrolled in the study. Two patients did not receive treatment because they were RAS mutant. Median age for the 44 treated patients was 76 years (range 70-88). Males were 32 and the PS was 0, 1 and 2 in 25%, 70.5% and 4.5% of patients, respectively. Rectal cancer accounted for 25% while 15.9% of patients had the primary tumour in situ. Twenty-one partial responses were observed for an ORR of 47.7% (95%CI: 32.9%-62.5%) while seven patients (15.9%) had stable disease. After a median follow-up of 36.0 months, the median progression-free survival was 6.1 months (95%CI: 3.6-8.7) and the median overall survival was 20.9 months (95%CI: 11.7-30.1). Grade 3-4 neutropenia was recorded in 4 (9%) and grade 3-4 diarrhea in 9 (20.4%) patients while one patient had a grade 4 bowel perforation. One patient experienced grade 3 mucositis, two patients grade 3 skin toxicity and two patients grade 3 fatigue. There were no toxic deaths while one patient died due to bowel obstruction and one due to postoperative complications after removal of the primary tumor. Conclusions: The modified FOLFIRI plus panitumumab combination presented significant efficacy with manageable toxicity in elderly patients with mCRC.

A phase II study of panitumumab with FOLFOX or FOLFIRI as first-line chemotherapy for KRAS-wild type metastatic colorectal cancer: The PaFF-J study.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 722-722 ◽  
Author(s):  
Eiji Shinozaki ◽  
Megumi Ishiguro ◽  
Eiji Nakatani ◽  
Tatsuro Yamaguchi ◽  
Masato Nakamura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Surgical Resection ◽  
Phase Ii ◽  
R0 Resection ◽  
Strong Impact ◽  
Tumor Shrinkage ◽  
Wild Type ◽  
Resection Rate ◽  
Line Chemotherapy

722 Background: For the patients with unresectable metastatic colorectal cancer (mCRC), response to the1st line chemotherapy has strong impact on their prognosis. Shrinkage of tumors may result in conversion to surgical resection and, concurrently, improved their survival. We conducted a multicenter phase II trial to investigate the efficacy and safety of panitumumab (Pmab) with chemotherapy as the 1st line treatment in Japanese patients with mCRC. Methods: Patients with no prior chemotherapy for unresectable, KRAS wild type mCRC, 20-80 years, and PS 0-1 were arbitrarily received either FOLFOX + Pmab or FOLFIRI + Pmab. Patients were evaluated every 8 weeks until progression. The primary endpoint was overall response rate (ORR), the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), R0 resection rate, and safety. Results: A total of 162 patients (140 with FOLFOX + Pmab and 22 with FOLFIRI + Pmab) were analyzed. Median follow-up was 28.2 months, median age at enrollment was 64.5 years, and 17.9% of the patients was recurrent disease. Number of target organ was 1 in 35.2%, 2 in 40.7%, and ≥ 3 in 24.1% of the subjects. Median administered cycle was 7, and median treatment duration was 16 weeks. ORR was 51.2% (95%CI: 43.3-59.2), and DCR was 82.1% (95%CI: 75.3-87.7). ≥ 30% tumor shrinkage (PR-in) was observed in 115 patients (71.0%). Median time to PR-in and maximum shrinkage was 10 and 16 weeks, respectively. Surgical resection was done in 66 patients (40.7%), of which R0 was in 43 patients; R0 resection rate was 26.5% (95%CI: 19.9-34.0). Median PFS and OS was 9.2 (95%CI: 7.2-11.4) and 33.8 months (95%CI: 29.4-43.1), respectively. ≥ Grade 3 adverse events with > 5% incidence were neutropenia (31.8%), stomatitis (10.5%), rash acneiform (9.9%), paronychia (9.3%), anorexia (8.6%), and diarrhea (6.2%). Conclusions: In our study, OS was favorable with high R0 resection rate, whereas ORR, DCR, PFS and toxicities were similar to those in previously reported studies. Because the maximum tumor shrinkage was observed around 16 weeks, optimal timing for considering conversion surgery might be 16 weeks from the start of treatment. Clinical trial information: UMIN000004991.

A phase II study of neoadjuvant immunotherapy combined with chemotherapy (camrelizumab plus albumin paclitaxel and carboplatin) in resectable thoracic esophageal squamous cell cancer (NICE study): Interim results.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4060-4060
Author(s):  
Zhigang Li ◽  
Jun Liu ◽  
Ming Zhang ◽  
Jinchen Shao ◽  
Yang Yang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Lymph Nodes ◽  
Neoadjuvant Therapy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
R0 Resection ◽  
Grade 3 ◽  
Initial Results

4060 Background: We conducted a phase II trial of preoperative chemotherapy with albumin paclitaxel and carboplatin combined with camrelizumab (NICE regimen), in patients with locally advanced esophageal squamous cell carcinoma (ESCC) with multiple lymph nodes metastasis. Initial results were analyzed to assess the efficacy and safety of this strategy. Methods: This was a prospective, multicenter, open, single arm, phase II trial. Eligible patients were histologically confirmed thoracic ESCC, staged as T1b-4a, N2-3 (≥ 3 stations), and M0 or M1 lymph node metastasis (confined to the supraclavicular lymph nodes) according to the 8th edition of American Joint Committee on Cancer. Patients received neoadjuvant treatment (NICE regimen) with intravenous camrelizumab (200 mg, day 1) plus albumin paclitaxel (100 mg/m2, day 1, 8, 15) and carboplatin (area under curve 5, day 1) of each 21-day cycle, for two cycles before surgery. The primary endpoint is pathological complete response (pCR) rate in the per-protocol population, which included all patients who had tumor resection and received at least one cycle of neoadjuvant treatment. Secondary endpoints include R0 resection rate, adverse events and disease-free survival. Safety was assessed in the modified intention-to-treat population. Results: Of the planned 60 patients enrolled, 55 (91.7%) patients have received the full two-cycles NICE regimen successfully, 4 patients didn’t receive the complete neoadjuvant therapy due to intolerance (3 patients) and drop out (1 patient), 1 patient died due to pneumonia on the second cycle of neoadjuvant therapy. Grade 3-5 treatment-related adverse events (TRAEs) rate was 53.3% and TRAEs resulting in discontinuation rate was 6.7%. The common grade 3-5 TRAEs included lymphopenia (50%), thrombocytopenia (10%), pneumonia (5%) and thyroid dysfunction (3.3%). At the time of writing, 47 patients underwent surgery within 27-85 days (median 36 days) after NICE treatment, in which 7 patients had delays to surgery due to TRAEs. All patients achieved radical (R0) resection. There was no in-hospital and postoperative 30-day mortality. pCR (ypT0N0) was identified in 20 (42.5%) of 47 patients and 5 (10.6%) patients had complete pathological response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). Conclusions: Preoperative NICE regimen has achieved satisfatory initial results of disease response in locally advanced thoracic ESCC. A phase III randomized controlled trial is required to demonstarate the possible survival improvement. Trial registration: ChiCTR1900026240 Clinical trial information: ChiCTR1900026240.

Phase II trial of DJ-927, an oral tubulin depolymerization inhibitor, in the treatment of metastatic colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3591-3591 ◽  
Author(s):  
M. R. Moore ◽  
C. Jones ◽  
G. Harker ◽  
F. Lee ◽  
B. Ardalan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peripheral Neuropathy ◽  
Metastatic Colorectal Cancer ◽  
Dose Reduction ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Grade 3

3591 Background: DJ-927, a novel oral tubulin depolymerization inhibitor, causes apoptosis and DNA cell division arrest. It is not a substrate for the MDR and has excellent activity in preclinical colorectal cancer models. Methods: We are conducting a two-stage, multi-center, phase II trial to assess the efficacy of DJ-927 administered initially as second-line therapy following failure of irinotecan or oxaliplatin based therapy (n= 39). DJ-927 is given as a single oral dose on day 1 of a 21-day cycle at a dose range of 27 - 35 mg/m2. Results: Thirty-nine patients were enrolled, including 14 with prior irinotecan based therapy and 25 who had received prior oxaliplatin therapy. The median age was 56 years (range: 30–87) and the median ECOG PS at baseline was 1 (range: 0–2). A total of 155 courses (range: 1–24) have been administered with a median of 2 courses. Nine patients required dose reduction due to toxicity. Thirty-seven patients were evaluable for efficacy. There were 2 CRs and 2 PRs (10.3%) reported that were confirmed as per RECIST criteria. Fourteen patients (35.9%) had SD, including 6 patients (15.4%) with SD >12 weeks. The most common Grade 3 or 4 AEs were neutropenia (48.7%), fatigue (10.3%), neuropathy (7.8%), and nausea (5.0%).Six patients experienced febrile neutropenia, all requiring hospitalization but tolerated treatment with subsequent dose reduction. There were 13 episodes (33.3%) of peripheral neuropathy reported; however, only 3 (7.8%) were grade 3 or 4. Six patients withdrew due to adverse events. Conclusions: The results of this study indicate activity of DJ-927 as second line therapy in patients with metastatic colorectal cancer. Severe toxicity was generally limited to reversible neutropenia and peripheral neuropathy. This novel oral agent is well tolerated and warrants further evaluation in combination with other active agents. [Table: see text]

Effect and safety of FOLFOXIRI+b-mab as preoperative chemotherapy for multiple liver metastases of colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14047-e14047
Author(s):  
Yasushi Ichikawa ◽  
Ayumu Goto ◽  
Takeshi Shimamura ◽  
Takashi Ishikawa ◽  
Jun Watanabe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Liver Metastases ◽  
Dose Escalation ◽  
Reduction Rate ◽  
Hematological Toxicity ◽  
R0 Resection ◽  
Resection Rate ◽  
Grade 3 ◽  
Multiple Liver Metastases

e14047 Background: R0 resection for liver metastases of colorectal cancer is one of the promising treatment to improve prognosis of advanced colorectal cancer. Recently, effective anti-cancer drugs and various regimens using them were created and some advanced inoperable liver metastases were converted to operable by these chemotherapy. Therefore, development of powerful regimens to shrink liver metastases strongly is an important issue. In our department phase I/II study of FOLFOXIRI+B-mab including fluoroiuracil/oxaliplatin/irinotecan/bevacizumab for advanced liver metastases of colorectal cancer as pre-operative chemotherapy has been conducted now. Methods: The study was designed as a single-arm, open-label phase I/II trial. Phase I was conducted as sequential dose escalation to define the maximum-tolerated dose (MTD) of irinotecan. Patients who are colorectal cancer with 4 or more liver metastases and no other distant metastases are included. The regimen includes bevacizumab; 5 mg/kg, oxaliplatin; 85 mg/m2, l-LV; 200 mg/m2, 5FU; 400 mg/m2 administered on day 1, followed by 5FU; 2400 mg/m2 continuously administered for 46 hours. Dose escalation of Irinotecan was planned from level 1; 150 mg/m2 , level 2; 180 mg/m2 and level 0; 125 mg/m2. In phase II, R0 resection rate of liver metastases as primary endpoint will be evaluated using MTD of irinotecan estimated in phase I. Results: Currently, 6 patients were studied. One patient showed grade 3 diarrhea as dose-limiting toxicity. For the other 5 patients, the study was accomplished. Grade 4 neutropenia was detected in 60%, however no patient showed febrile neutropenia. Excluding hematological toxicity, grade 3 or worse adverse event was only one grade 3 diarrhea described above. All 5 patients were performed R0 resection. All 5 patients showed PR and average of reduction rate was 62.7%. There was no pathological CR in the 5 patients who was performed R0 resection. There was no severe postoperative complication in them. Conclusions: This regimen is safe and shows high PR rate. So, the regimen is effective and improve R0 resection rate for multiple liver metastases of colorectal cancer. Further investigation of this study is still ongoing now.

A phase II study of neoadjuvant chemotherapy with bevacizumab plus mFOLFOX6 for resectable synchronous liver metastasis (SLM) from colorectal cancer: The first report of the Miyagi Hepato-Biliary Pancreatic Clinical Oncology Group.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 593-593
Author(s):  
Yu Katayose ◽  
Junichiro Yamauchi ◽  
Masaya Oikawa ◽  
Naoki Sakurai ◽  
Hiroaki Musya ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Liver Metastases ◽  
Phase Ii ◽  
Initial Treatment ◽  
Phase Ii Study ◽  
University Hospital ◽  
R0 Resection ◽  
Liver Resections ◽  
Grade 3

593 Background: The prognosis of synchronous liver metastases (SLM) from colorectal cancer is poor. Therefore, we conducted a phase II study of neoadjuvant chemotherapy for SLM to determine the appropriate initial treatment. Here, we assessed the effectiveness of bevacizumab combined with mFOLFOX6. Methods: Patients with SLM within 10 nodules were enrolled after R0-resection of the primary colorectal cancer, and received 8 courses of mFOLFOX6 with bevacizumab (the first and last courses were mFOLFOX6 only). The primary endpoint was response rate (RR). Results: Between June 2008, and November 2008, 47 patients (pts) were enrolled from 17 centers. The median age was 62 years (range 32-72 yrs). The median number of metastases was 2 nodules. Three pts were excluded from evaluation of RR because they did not receive any scheduled chemotherapy. The RR was 70.5% (2 complete responses and 29 partial responses). 11 pts (25%) showed stable disease and 2 pts (4.5%) had progressive disease. The liver resections rate was 90.9% (40 pts) and the R0-resection rate was 86.3%(38 pts). Adverse events in order of prevalence were sensory neuropathy, neutropenia, hypertension, leucopenia and so on. Grade 3 and 4 AEs occurred in 21 pts with the most common being Neutropenia. There were 3 Grade 4 AEs: renal failure and 2 pts of neutropenia. Grade 3 or 4 AEs are summarized below. There were no grade 5 AEs. Of note, liver resections were safely performed in the three pts with Grade 4 AEs. Conclusions: Neoadjuvant chemotherapy with bevacizumab plus mFOLFOX6 for liver metastases is effective and well tolerated. The benefit of this therapy as the initial treatment of SLMneeds to be evaluated further by comparison with adjuvant therapy. (This trial is on University hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR). UMIN's unique trial number is UMIN000001568.) [Table: see text]

Did neoadjuvant chemotherapy provide better long term outcomes in borderline resectable with arterial involvement (BR-A PC)?

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 434-434
Author(s):  
Kei Saito ◽  
Yousuke Nakai ◽  
Yoshihiro Sakamoto ◽  
Kazunaga Ishigaki ◽  
Naminatsu Takahara ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Palliative Chemotherapy ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
R0 Resection ◽  
Long Term Outcomes ◽  
Resection Rate ◽  
Arterial Involvement

434 Background: Recently high rates of conversion (or adjuvant) surgery were reported after neoadjuvant chemo(radiation)therapy (NAC) for borderline or locally advanced pancreatic cancer (BR/LA PC) including our phase II trial of gemcitabine, S-1 and leucovorin (GSL) combination therapy for BR PC with arterial involvement (BR-A PC) and LA PC. In our phase II trial, a high recurrence rate of 78% was noted despite a high R0 resection of 76%. Herein, we conducted a retrospective analysis of BR-A PC who underwent NAC, upfront surgery and palliative chemotherapy to evaluate the long term outcomes of NAC. Methods: Consecutive patients with BR-A PC at the University of Tokyo Hospital were retrospectively studied. Clinical outcomes in patients who underwent (NAC group) were compared with those in patients who underwent upfront surgery or palliative chemotherapy (non-NAC group). NAC was introduced in our institution from January 2014. Results: A total of 45 patients (22 non-NAC and 23 NAC group) were diagnosed with BR-A PC between January 2008 and December 2016. There were no significant differences in patient characteristics between non-NAC group and NAC group: Median age of 63 vs. 64, male in 72% vs. 52%, Performance status of 0 in 63% vs. 65%, median pretreatment CA19-9 of 175 vs. 205 U/ml. In non-NAC group, 17 underwent palliative chemotherapy as follows 8 gemcitabine alone, 3 gemcitabine and S-1 combination chemotherapy and 6 other regimens. The remaining 5 patients underwent upfront surgery with an R0 resection rate of 80%. In NAC group, a median duration of neoadjuvant chemotherapy was 4 months. A total of 14 patients underwent surgical resection with an R0 resection rate of 76%. The remaining 9 patients had disease progression during NAC and received 2nd line chemotherapy. The median follow-up time was 16.5 months in non-NAC group and 15.3 months in NAC group. The median overall survival (OS) were 19.3 vs. 21.9 months (p = 0.25). Conclusions: Both R0 resection rate and the median OS were comparable between non-NAC group and NAC group. An ideal regimen of NAC or its duration needs further investigation to prolong OS in BR-A PC.

Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous infusion in metastatic colorectal carcinoma.

1997 ◽  
Vol 15 (8) ◽  
pp. 2905-2909 ◽  
Author(s):  
R Pazdur ◽  
E Diaz-Canton ◽  
W P Ballard ◽  
J E Bradof ◽  
S Graham ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinoma ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Anticancer Agents ◽  
Phase Ii Trial ◽  
Human Tumor ◽  
Clinical Activity ◽  
Metastatic Colorectal Carcinoma ◽  
Grade 3

PURPOSE The camptothecin derivative irinotecan has demonstrated clinical activity in metastatic colorectal carcinoma in both chemotherapy-naive and fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another camptothecin derivative, was selected for clinical development based on preclinical activity, including cures in human tumor xenografts resistant to standard anticancer agents. We report a phase II trial of 9-AC in patients with previously untreated metastatic colorectal carcinoma. PATIENTS AND METHODS Colorectal cancer patients with measurable disease, a performance status of 0 to 2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC. A cycle of therapy was 35 microg/m2/h for 72 consecutive hours (840 microg/m2/d for 3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles (28 days). Patients were assessed for response after two courses. RESULTS Seventeen patients with metastatic colorectal cancer were entered onto this trial. No complete or partial responses were noted. Treatment was well tolerated; toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis, fatigue, and anemia. Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients had their 9-AC dose reduced to 30 microg/m2/h. The median nadir absolute granulocyte count (AGC) was 1,500/microL. The median number of courses given was two and the median time to disease progression was 8 weeks. CONCLUSION At the dose and schedule used in this trial, 9-AC lacked antitumor activity in metastatic colorectal cancer. 9-AC infusion schedules of longer duration are currently being investigated in this disease.

Sign in / Sign up

Export Citation Format

Share Document