bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critical evaluation of the role of oxaliplatin- and irinotecan-based regimens as first-line chemotherapy in advanced colorectal cancer (CRC)
Authors: Carnaghi C. , Rimassa L. , Zuradelli M. , Morenghi E. , Torri V. , Tronconi M. C. , Pressiani T. , Santoro A. 
Published: March 2020

13562 Background: Until recently, 5-fluorouracil (5-FU) has been the mainstay of treatment for advanced CRC. In the last years, irinotecan and oxaliplatin have been shown to improve survival in combination with 5-FU. It is unclear if this improvement requires the use of these agents as first-line treatment or their sequential use during the course of disease. Methods: In order to assess the impact on prognosis of the first-line chemotherapy regimen, we retrospectively reviewed the outcome of all patients (pts) with advanced CRC treated at our insitution from May 1997 to December 2003. During this period our standard first-line chemotherapy moved from 5-FU and folinic acid (FA) to FOLFIRI to FOLFOX regimens. We analyzed changes in overall survival over time according to administered treatments. Results: From May 1997 to December 2003, 376 consecutive pts with advanced CRC were treated at our institution, 118 from 1997 to 1999, 135 from 2000 to 2001, 123 from 2002 to 2003. Patient characteristics did not vary over time for the 3 cohorts: median age was 62 years (range 26–83), 58% of pts were male, 72% had single metatastic site, liver was the main disease site (72%). In the first cohort (1997–99) the standard first-line treatment was 5-FU/FA, in the second (2000–01) FOLFIRI, and in the third (2002–03) FOLFOX. The number of pts who underwent 1, 2 o 3 lines of treatment for metastatic disease was similar for the 3 cohorts. The median overall survival was 21.4 months (95% CI 19.3–23.3). As shown below, no statistically significant differences were observed among the cohorts. Conclusions: Our retrospective analysis shows that the use of oxaliplatin and irinotecan has pushed the overall median survival to 21 months. The outcome of pts has been similar during the period 1997–2003 despite the shift in standard first-line treatment from 5-FU/FA to FOLFIRI to FOLFOX. These results are reasonably due to the sequential use of all the active regimens. [Table: see text] No significant financial relationships to disclose.
Retrospective review of toxicities and response of two commonly used regimens (FOLFOX6 and XELOX) in stage IV colorectal cancer
Authors: Mullane M. , Lad T. , Cleveland B. , Yim B. , Tamkus D. , Osafo D. 
Published: March 2020

13568 Background: Oxaliplatin and 5FU based regimens have become standard first line treatment for stage IV colorectal cancer. At our institution predominately the regimens FOLFOX6 (oxaliplatin/infusional 5FU via a central venous catheter) and XELOX (oxaliplatin/ capecitabine given orally) are used. We performed a retrospective review of 40 patients to see if any differences, primarily in toxicities, but also in response, emerged. Methods: . Twenty consecutive patients with Stage IV colorectal cancer who received FOLFOX6 as initial therapy and twenty consecutive patients who received initial XELOX, with the oxaliplatin given via a peripheral IV, were analyzed. The decision to administer FOLFOX6 or XELOX was not made for clinical reasons, but came about from logistical difficulties placing central venous catheters in our institution, due to cost and operating time. Comparisons were performed with a Mann Whitney test. The two groups were well matched in terms of sex, age, and performance status. Response evaluations were made based on RECIST criteria. Results: Toxicities compared in the two groups (FOLFOX6 v. XELOX) were gastrointestinal, >Gr. II (5 v. 20%); dermatologic, >Gr. III (0 v. 35%); bone marrow, > Gr. II (15 v. 20%); neurologic, >Gr. III peripheral neuropathy (10 v. 10%); and development of arm pain/discomfort (0 v. 30%). The two toxicities reaching a significant difference, with the higher incidence from XELOX, were > Grade II dermatitis (p= 0.03) and development of arm pain (p=0.05). The response rate of FOLFOX6 was 75% and that for XELOX was 55% (p value of 0.144). Conclusions: Our conclusions from this analysis are that the two regimens are comparable in terms of response, but that FOLFOX6 may be preferable in order to avoid severe dermatitis and if XELOX is the treatment choice, serious consideration should given to administer the oxaliplatin via a central catheter. No significant financial relationships to disclose.
In-depth analysis of high effectivity in phase II study (irinotecan and doxifluridine, an intermediate form of capecitabine) for metastatic colorectal cancer: MCSGO, Colorectal Cancer Treatment Group
Authors: Kato T. , Miyake Y. , Ikenaga M. , Mishima H. , Fukunaga M. , Murata K. , Ota H. , Sekimoto M. , Sakamoto J. , Monden M. 
Published: March 2020

13570 Background: We have already reported the results of the Phase II multicenter study [a combination of irinotecan (CPT-11) and doxifluridine (5’-DFUR) for MCRC], including the survival period (2006 GI Cancer Symposium Abst #130). In this report, we mention the details of the treatment introduced after this combination and discuss the response observed in each metastatic lesion. Methods: The subjects were 60 CPT-11 naive patients with MCRC. They had a measurable disease that satisfied the RECIST criteria and had gone through not more than one regimen of chemotherapy (median age: 64 years (28–74); male/female: 37/23; ECOG PS 0/1: 52/8; main location of metastatic lesion: liver 31, lung 13, lymph node 15). CPT-11 (150 mg/m2, i.v.) was administered on days 1 and 15, 5’-DFUR (800 mg/body, p.p.) was administered day 3 to 15 and day 17 to 28. One cycle of treatment consisted of 5 weeks. No requirements were imposed on the follow-up treatment. Results: According to the results of this regimen, ORR was 40% [23/60, CR;1, PR;23], OS was 20.5 months, and PFS was 5.9 months. The main NCI-CTC grade 3–4 adverse events included neutropenia (28.3%), fatigue (11.6%), nausea (8.3%), vomiting (6.6%), and diarrhea (5.0%).A follow-up therapy regimen was selected and implemented by each investigator. The main regimens adopted for the 49 patients who received this combination as a 1st line therapy included FOLFOX (n=10), hepatic arterial infusion (HAI) (n=10), and others (n=13). 16 patients received no follow-up therapy. The duration of treatment was 5.0 months in the case of 2nd line therapy and 3.0 months in the case of 3rd line therapy. The response rate by metastatic lesion was as follows: liver 35.4% (11/31, PR;11), lung 53.5% (7/13, CR;1, PR;6), and lymph node 46.6% (7/15, PR;7). Conclusions: The combination of CPT-11 and 5’-DFUR is effective in treating lung metastasis and HAI in treating liver metastasis was suggested. No significant financial relationships to disclose.
Phase II clinical trials of combination S-1 plus low-dose twice weekly cisplatin for advanced or recurrent gastric cancer
Authors: Tsuji A. , Morita S. , Uchida M. , Okamoto K. , Morita M. , Horimi T. 
Published: March 2020

14013 Background: We reported the efficacy and safety of combined S-1 + low-dose consecutive cisplatin therapy for advanced or recurrent gastric cancer (Clin Cancer Res. 10:1664–9, 2004). However, this procedure was complicated because the daily dosage of CDDP was necessary. We confirmed that 6 mg/m2 dosage of twice weekly Cisplatin were maintained equal protein binding Pt concentration after daily treatment of 3 mg/m2 dosage of Cisplatin. We examined an effect and safety of a Combination S-1 plus low-dose twice weekly Cisplatin treatment. Methods: All the subjects were admitted to the hospital as inpatients for the first 2 weeks of therapy. S-1 was administered orally daily at the daily dose level of 80 mg/m2 (administered in two divided doses). Cisplatin 6 mg/m2 was administered by intravenous drip infusion over 30 minutes on 2days of the week (Day1 and Day4). Each treatment cycle consisted of 4 weeks of drug administration followed by a 2-week drug-free period (6 weeks in total). Results: 32 patients were enroled in this study. The response was rated as complete response in 1 case, partial response in 24 cases and stable disease in 5 cases. The response rate was 78.1% (25/32). The median survival time was 10.3 months. The response rate did not differ between previously untreated patients and patients who had received prior treatment. The major adverse reactions to the therapy were bone marrow suppression and gastrointestinal symptoms. The total incidence of grade 3 or more severe adverse reactions was 15.6% (5/32). Conclusion: Combination S-1 + low-dose twice weekly Cisplatin therapy thus appears to be highly efficacious and safe, offers promise as a useful treatment strategy even at outpatient clinics. [Table: see text] No significant financial relationships to disclose.
Oxaliplatin/CF/5-FU versus paclitaxel/CF/5-FU in patients with advanced gastric cancer: A phase II clinical trial
Authors: Lin T. , Xu F. , Wang S. , He Y. , Tian W. , Guan Z. 
Published: March 2020

14014 Background: Although many randomized trials of chemotherapy for advanced gastric cancer have been reported during the past two decades, no standard regimens worldwide have been established yet. Now Paclitaxel and Oxaliplatin have shown promising activity in advanced gastric cancer. We prospectively evaluated toxicity, efficacy and survival of Oxaliplatin /CF/5-FU versus Paclitaxel/CF/5-FU. Methods: Metastatic or locally advanced gastric cancer; performance status (PS) 0–2. Patients (pts) were enrolled and randomized into arm A with Oxaliplatin 100mg/m2, 5-FU 400 mg/m2 bolus, FA 200 mg/m2 2h, 5-FU 2500 mg/m2 46h, q2w or into arm B with Paclitaxel 80 mg/m2, 5-FU 400 mg/m2 bolus, FA 200 mg/m2 2h, 5-FU 2500 mg/m2 46h, q2w. Results: From 2000 to 2005, (A/B) 46/43 pts were enrolled into this study. Median age (52/50 y), gender, PS, localization and numbers of metastatic sites were comparable for both arms. Pts who were not chemotherapy naive in A/B (% of pts) were 41.3/33.3. All pts were eligible and evaluable for toxicity and response. Overall response (CR+PR) rate for A/B (% of pts): 37.0/47.2 (p<0.05), tumor control rate (CR+PR+SD) 76.1/69.4(p<0.05). Median time to progression (TTP) were for A/B: 6.0 and 3.2 months. And median survival time for A/B were 13.4 and 13.8 months. Grade 3/4 toxicities were for A/B (% of pts): neutropenia 10.9/5.6, thrombocytopenia 4.3/2.8, anemia 0/2.8, vomiting 8.7/2.8, neurotoxic 0/2. No treatment-related death occurred in A/B. Conclusions: Oxaliplatin /CF/5-FU and Paclitaxel/CF/5-FU are both effective and safe in advanced or metastatic gastric cancer. Though Oxaliplatin /CF/5-FU had better tumor control rate and median TTP, there was no difference between the arms in the median survival time. No significant financial relationships to disclose.
A phase II study of alternating chemotherapy with CDDP/ 5FU/ folinic acid (FA) and epirubicin (E)/ docetaxel (T) (CF-ET regimen) as first line therapy for patients (pts) with metastatic gastric cancer (MGC)
Authors: Kirchner H. H. , Panagiotou P. , Jordan O. , Hamann S. , Sosada M. 
Published: March 2020

14021 Background: Active single agents in MGC are 5FU, CDDP, Anthracyclines, Taxanes and irinotecan. Combinations consisting of docetaxel, cisplatin, 5FU (TPF) and epirubicin, cisplatin, 5FU (ECF) have been investigated and both have shown activity and improvement of survival. However, the most efficient regimen is not yet defined. Methods: Chemotherapy-naive Patients with histologically confirmed MGC and measurable lesions were enrolled in this study. They received CDDP 35 mg/m2 iv on day (d) 1, 2, 15 and 16, 5FU 2000 mg/m2 continuous infusion (ci) d 1, 8, 15 and 22, FA 200 mg/m2 iv d 1, 8, 15 and 22 and E 60 mg/m2 d 29 and 43, T 60 mg/m2 d29 and 43 q d 57. Pts with at least one completed cycle were eligible. Objectives of this study were to evaluate the response rate, toxicity, PFS and OAS of CF-ET. Results: Between 2002 and 2005 34 pts (22 male and 9 female) aged 31 - 77 years (median 61) entered. The total number of treatment cycles was 56, mean 1.8 (1 - 5). 31 pts were eligible. 9 pts had complete response; 11 pts had partial response, 4 pts had stable disease, 7 pts had progressive disease and 3 pts were not evaluable. The overall response rate was 64.5%. The median response duration was 6.1 months (2 - 29.4). The overall survival was 11.4 months (2.6 - 43.6). Grade 3/4 toxicities were leukopenia 41/37.5%, neutropenia 16/82%, thrombocytopenia 23.2/0%, neutropenia related fever was observed in 4 cycles. No severe organ toxicities nor toxic death was seen. Conclusions: The alternating CF-ET regimen showed significant efficacy with prolonged survival. The ET-part of the regimen induced severe but manageable haematological toxicities. The results require further evaluation in a randomized phase III - trial. No significant financial relationships to disclose.
Phase II study of a combination of S-1 and weekly paclitaxel in patient with advanced or recurrent gastric cancer
Authors: Ueda Y. , Yamagishi H. , Ichikawa D. , Morii J. , Kakihara N. , Yamashita T. , Aragane H. , Nishi H. , Chigusa A. , Sakamoto J. 
Published: March 2020

14033 Background: Based on the results of our phase I study on a combination of S-1 (tegafur, oxonic acid, and CDHP) and weekly paclitaxel (PTX) for advanced or recurrent gastric cancer (ARGC) (Ueda et al, ASCO 2004), we conducted a multi-center phase II study to prospectively evaluate efficacy, QOL, and toxicity of S-1 plus weekly PTX in patients with ARGC. Methods: Eligibility included patients with histologically-proven ARGC, 20–80 years old, having a ECOG performance status (PS) of 0–2 and adequate organ functions, and having received no prior chemotherapy except postoperative adjuvant therapies without taxanes. S-1 was given orally at a dose of 80 mg/m2/day for 14 consecutive days (days 1–14) followed by a 2-week rest. PTX was administered weekly as a 1-hour intravenous infusion on days 1, 8, and 15. This treatment was repeated every 4-weeks as one cycle. Results: Fifty-four patients with measurable lesions (RECIST) were enrolled between Feb. 2004 and Nov. 2005. Histologically, a half of the patients had differentiated type and the other patients had undifferentiated type adenocarcinoma. The median age was 61 (range, 38–78). Three-fourths were male patients. The PS was 0/1/2 in 47/6/1 patients respectively. Thirty nine were primary cases and 15 were recurrent cases after gastrectomy. Treatment was terminated in two patients for toxicities and in one patient for refusal during the first cycle; thus compliance of 94.4%. A total of 254 cycles were administered (median 4.7, range 2–14), and 45 patients were assessable efficacy and toxicity until Dec. 2005. In these 45 assessable patients, 2 CRs and 27 PRs were obtained, resulting in an overall response rate of 64.4%. Twelve pts (26.7%) had stable disease, and 4 pts (8.9%) progressed. The tumor control rate was 91.1%. Conclusions: The combination of S-1 and weekly PTX is highly active for ARGC, and can be given safely with good tolerance and convenience profile. It is a candidate for the standard regimen and expected to contribute to better prognosis and QOL in ARGC patients. No significant financial relationships to disclose.
A phase II trial of the epothilone B analog BMS-247550 in patients (pts) with hepatobiliary cancer (HBC): An updated analysis
Authors: Singh D. A. , Taber D. , Ansari R. , Lenz H. J. , Agamah E. , Nattam S. , Wade-Oliver K. , Kasza K. , Vokes E. E. , Kindler H. L. 
Published: March 2020

14050 Background: BMS-247550 is a semi-synthetic analog of epothilone B that induces mitotic arrest at G2M by microtubule stabilization. We previously reported (Proc ASCO 2003) a RR of 17% in HBC and present our final analysis. Methods: Pts with histologically confirmed hepatocellular cancer (HCC), gallbladder cancer (GB) and cholangiocarcinoma (C) were eligible. Pts had no prior chemotherapy, PS 0–2 and ≤ grade 1 neuropathy. Pts received BMS-247550 40mg/m2 intravenously over 3 hours every 21 days. A Simon, optimal two-stage design was employed. We proceeded to the 2nd stage of accrual after 3 confirmed PRs in the first 21 pts. Primary endpoint: Response rate (RR). Results: From 1/02–4/05, 54 pts (52% male) were enrolled, 53 pts evaluable for toxicity, 48 pts evaluable for response. 1 pt was ineligible due to incorrect diagnosis but evaluated for toxicity. Pt characteristics: median age 65 (range 19–88); ECOG performance status 0(48%), 1(48%), 2(4%); HCC (38%), GB (40%), C (22%); metastatic disease (75%); 129 cycles were administered (median 2; range 1–14). There were 3 Gr 5 toxicities: 1 pt died unexpectedly 48 hours within drug administration; 1 complication of neutropenic fever; 1 found unresponsive after fall. Gr 3–4 toxicities (% pts): neutropenia (39%), neutropenic fever (6%), anemia (6%), thrombocytopenia (2%), nausea (13%), transaminase elevation (9%), fatigue (7%), and hypersensitivity (4%). Neuropathy: Gr 3–4 (5%); Gr 1–2 (39%). 3 pts were removed from study due to persistent neuropathy. Responses: 8% PR (2 HCC, 1 GB, 1C); 56% SD. 4/7 HCC pts received ≥ 10 cycles. Median survival: 7 months [95% CI (5.0, 10.8)]; PFS: 2.6 months [95% CI [1.4, 4.1)]; Conclusions: Despite initial tumor responses and a few pts with prolonged SD in HCC, BMS-247550 does not appear to have clinically significant activity in HBC. Supported by NCI grant N01-CM-17102. [Table: see text]
Pilot study of capecitabine combined with celecoxib (CapCel) as second-line treatment for advanced pancreatic (P) and biliary tree (BT) cancer
Authors: Gelibter A. , Milella M. , Malaguti P. , De Marco S. , Ruggeri E. , Carlini P. , Pino M. , Nuzzo C. , Sternberg C. N. , Cognetti F. 
Published: March 2020

14055 Background: COX-2 is overexpressed during cancer progression in several solid tumors, including P and BT, and constitutes an attractive therapeutic target. Selective COX-2 inhibitors, such as celecoxib, have been successfully combined with fluoropyrimidine-based regimens, resulting in a lower-than-expected hematologic, GI, and skin toxicity rate. Methods: Advanced P or BT patients (pts), progressing after first-line treatment, were eligible for the study. Capecitabine was administered at 1000 mg/m2 b.i.d. on days 1–14 q3 weeks; celecoxib was administered at 200 mg b.i.d. continuously starting on day 1. PFS was the primary endpoint. ORR, toxicity, OS, clinical benefit (CB), and QoL were secondary endpoints. Assuming that a rate of PFS >15% at 3 mos would be considered of interest in this pt population, an accrual of 28 pts was planned according to the exact single-stage phase II design described by A’Herne. Results: To date, 25 pts have been accrued (M/F: 11/14; median age: 64 yrs, range 39–75; P/BT: 18/7; PS 0–1/2–3: 19/6). All pts completed at least 1 treatment cycle (median: 3, range 1–9). Twenty-three pts are currently evaluable for response: 1 PR and 1 MR (duration: 33 and 27+ wks) were observed, both in pts with P; 5 additional pts showed SD (duration: 10+, 21, 22+, 27, and 42 wks); the remaining 16 pts had PD. All pts and 83 cycles are evaluable for toxicity. Hematological toxicity was negligible; only 4 pts experienced G3 non-hematological toxicities: diarrhea (2 pts, 2 cycles), skin toxicity (1 pt, resolved with treatment delay), asthenia (1 pt, 2 cycles), and GI bleeding (1 pt, requiring treatment interruption after cycle 1). To date, 19 pts have progressed and 15 pts have died: median PFS is 11 wks (range 3–42) and median OS is 16 wks (range 4–54). Nineteen pts had elevated CA19.9 serum levels at baseline, which decreased of > 25% during treatment in 7 pts, remained stable in 3 pts, and increased in 9 pts. The evaluation of CB and QoL is ongoing. Conclusions: CapCel is a feasible and well-tolerated, fully oral, treatment regimen for advanced P and BT patients, which shows activity, albeit modest, even in a second-line setting. Further evaluation of this therapeutic strategy is warranted. No significant financial relationships to disclose.
Cetuximab, intensity-modulated radiotherapy (IMRT), and twice-weekly gemcitabine for pancreatic adenocarcinoma
Authors: Pipas J. M. , Zaki B. , Suriawinata A. A. , Tsapakos M. J. , Ripple G. H. , Colacchio T. A. , Sutton J. E. , Gordon S. R. , Kasibhatla M. S. , Barth R. J. 
Published: March 2020

14056 Background: Epidermal growth factor receptor (EGFR) is over expressed in pancreatic cancer. Cetuximab is an EGFR-antagonist which has synergy with gemcitabine (gem) and radiation. Gem is a potent radiosensitizer. We are conducting a Phase II trial of cetuximab with IMRT and twice-weekly gem. Eligibility includes stage I-III adenocarcinoma, with EGFR staining by immunohistochemistry. Pretreatment evaluation includes chest/abdomen CT scan and laparoscopy. Methods: Cetuximab 400 mg/m2 IV load was given over two hours. One week later, treatment continued with weekly cetuximab 250mg/m2 IV over one hour, and gem 50mg/m2 IV twice-weekly for twelve doses, concurrent with IMRT given in 28 daily fractions to 54Gy. Cetuximab/gem was given prior to that day’s IMRT. GI prophylaxis was with a proton pump inhibitor. Patients were considered for resection 4–8 weeks following therapy. Results: Ten patients enrolled to date, median age 70 years (range 54–83). Ninety percent of tumors were EGFR positive (range 1+ to 3+). At presentation, three tumors were unresectable, three borderline resectable and four resectable. One patient was removed from study following cetuximab anaphylaxis. Eight patients experienced grade III-IV hematotoxicity. Two patients had ischemic stroke in the backdrop of infection, one from stent obstruction/cholangitis, the other during neutropenic fever. One of these patients (age 81) died. Autopsy revealed severe atherosclerotic disease and evidence of prior strokes. Eight patients were evaluable for response. No patient had local progression. One patient had liver metastases post treatment. Two patients (25%) exhibited partial response. All others had stable disease. EGFR over expression did not predict response. Six patients went on to margin (−) resection, including one patient each with borderline resectable and unresectable disease prior to therapy. At median follow up of 8.5 months, there were no recurrences. Conclusions: Therapy yields modest efficacy and high resectability rates in patients with pancreatic cancer. Downstaging of tumor can occur in some patients. Toxicity may in part reflect the elderly patient demographic. Planned accrual is 48 patients. [Table: see text]