bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical features of ulcerative colitis-associated colorectal cancer in Japan: an analysis of 169 cases over 20 years
Authors: Watanabe T. , Konishi T. , Muto T. , Kotake K. , Nagawa H.
Published: March 2020

13544

Background: Development of colorectal cancer is a well-known long-term complication of ulcerative colitis (UC). However, specific clinical features of UC-associated colorectal cancer have been controversial mainly due to the small number of cases, especially in the Asian countries. This study aims to clarify the clinicopathological features of UC-associated colorectal cancer compared with non-UC-associated colorectal cancer in Japan, using a large nationwide database. Methods: All patients pathologically diagnosed as colorectal cancer from 1978 to 1998 were extracted from the nationwide database, “Multi-Institutional Registry of Large-Bowel Cancer in Japan”, which covers almost 10% of all colorectal cancers in Japan. Clinicopathological factors were compared between those associated with UC and the others. Survival analysis in each TNM stage was performed using the Kaplan-Meier method. Results: Among 108,536 cases of colorectal tumors registered from 1978 to 1998, a total of 169 cases of UC-associated colorectal cancers were identified. All cases were from the Asian population. UC-associated cases showed higher prevalence of females, younger age, higher incidence of multiple cancers, and higher incidence of mucinous adenocarcinomas. On the other hand, there were no differences in tumor sites, family history of colorectal cancer, lymph node metastasis, distant metastasis, TNM stage, and CEA level adjusted by TNM stage between the two groups. Survival analysis revealed poorer prognosis in UC-associated colorectal cancers at TNM stage 3. Conclusions: UC-associated colorectal cancer showed unique histological features compared with usual colorectal cancer. The survival of UC-associated colorectal cancer with lymph node metastasis was poorer than usual colorectal cancer, and therefore, intensive adjuvant therapy and close follow-up is needed after surgery in this patient group.

No significant financial relationships to disclose.
Does serum VEGF predict prognosis in metastatic colorectal carcinoma patients treated with XELIRI?
Authors: Bozcuk H. S. , Artac M. , Akcan S. , Korgun D. K. , Ozben T. , Ozdogan M. , Samur M. , Mutlu H. , Kargi A. , Savas B.
Published: March 2020

13548

Background: Serum vascular endothelial growth factor (sVEGF) levels have been shown to possess prognostic value in different solid tumors. However, there is no solid information on the prognostic use of sVEGF in metastatic colorectal carcinoma (MCRC) patients treated with a standard regimen. Methods: 37 consecutive MCRC patients were given XELIRI chemotherapy as the 1st line treatment (irinotecan 250 mg/m2 on day one, and Capecitabine 2000 mg/m2/day, for 14 days starting on day1, repeated in every 3 weeks). Serum VEGF levels prior to the 1st cycle of chemotherapy was measured by ELISA. Kaplan-Meier survival curves and Cox regression analyses to adjust for basic clinical features were used for the survival analysis. Binary logistic regression analysis was employed to determine correlates of objective response (CR+PR). Results: Best objective response was CR+PR in 20/33(61%) cases (3 CR; 9% + 17 PR; 52%). In 4 patients, response assessment was not possible. Median sVEGF was 650(107–1865) pg/ml. Median OAS and PFS was 16.2 and 5.9 months, respectively. Increased age turned out to be the only predictor of better OAS with borderline significance (P=0.09). After adjustment for performance status (0, 1 versus 2) and disease extent (single vs. multiple metastatic sites), age was statistically significant (P=0.042, HR=0.95(0.90–0.99)). For PFS, again age (P=0.038) was the only correlate. After controlling for performance status and disease extent, age (P=0.014, HR=0.95(0.92–0.99)) and performance status (P=0.036, HR=3.27(1.08–9.88)) were significant. No factor was associated with the likelihood of objective response. Conclusion: In this study, we failed to determine any prognostic value for sVEGF in MCRC. However, older age and good performance status appear to have a borderline positive prognostic value for MCRC patients treated with XELIRI.

No significant financial relationships to disclose.
Biweekly treatment with bevacizumab (BV) as 2nd line chemotherapy in patients with metastatic colorectal cancer
Authors: Samelis G. F. , Areovimata A. , Adrachta D. , Palazi A. , Papagianni V.
Published: March 2020

13561

Background: Bevacizumab (BV), a monoclonal antibody directed against vascular endothelial growth factor, provides a survival advantage (15.6 to 20.3 months) when added to first-line chemotherapy for metastatic colorectal cancer (metastatic CRC). Only a few trials have been conducted using BV as 2nd line chemotherapy. Methods: Sixteen patients with metastatic CRC refractory to first-line chemotherapy (oxaliplatin or irinotecan-based regimen) were enrolled. All patients, after progressing in first-line treatment, received the following regimen: BV: 5 mg/Kg* in 1000ml water for injection in 90min IV infusion plus irinotecan 125mg/m2 IV in 500ml NIS in 60min plus folinic acid 30mg/m2 and 5-fluorouracil 500mg/m2 IV bolus infusion. The schedule was repeated every 2 weeks. Fourteen men and 2 women entered the study with PS 0–1, median age of 66 years (range: 48–85). 11 patients (68.7%) had liver metastases, 3 patients (18.75%) had lung metastases and 4 patients (25%) had local tumor recurrence. All 16 patients were eligible for the study and received in total 174 (mean 10.8, range: 6–20) cycles. Six out of 16 patients (12.5%) had more than 2 metastatic sites (liver and local recurrence). Results: Six patients had partial responses (PRs) (37.5%), 4 patients had stable disease (SD) (25%) and the rest of the patients progressed (37.5%). The time to progression (TTP) was 6.4 months (range: 4–8), and the median survival was 9 (range: 5–12) months. The toxicity was mild and no toxic death was reported. Grade II toxicities were the following: epistaxis 4 patients (25%), anaemia 5 patients (31%), leukopenia 3 patients (18.7%), granulocytopenia 2 patients (12.5%) and 1 patient developed jaundice due to bile-duct obstruction. Conclusions: The bi-weekly administration of BV, irinotecan, leucovorin and 5-fluororacil is acceptable as 2nd line treatment in patients with metastatic CRC, with an overall response rate (PRs) of 37.5%, and SD of 25%. The TTP and survival were 6.4 and 9 months respectively. The study is ongoing and we expect to enrol more patients.

No significant financial relationships to disclose.
Capecitabine combined with Irinotecan (CapIri) as first line treatment of advanced colorectal carcinoma (ACRC): A phase ll study
Authors: Zidan J. , Basher W. , Shnaider J. , Tmam S. , Abzah A. , Chetver L.
Published: March 2020

13569

Background: The combination of 5-FU + LV with irinotecan as first line treatment of advanced colorectal cancer (ACRC) has shown higher response rate compared with 5-FU +LV with the same progression free survival. Capecitabine is more active than 5-FU.The aim of this study is to determine the side-effect profile, dose limiting toxicity and response rate to CapIri combination as first line treatment in ACRC, on an outpatient basis. Methods: Inclusion criteria: age >18–75 years, ECOG ≤ (0–3), measurable disease, no previous treatment for advanced disease, previous adjuvant chemo-therapy more than 6 months is allowed, signed informed consent and adequate hepatic, renal and hematological function. Exclusion criteria: Serious concurrent medical disorders, prior other malignancy, pregnancy or breast-feeding and patients with poor compliance. Capecitabine 1000mg/m2 twice daily was given for 14 days followed by 7 days rest and Irinotecan (100mg/m2) was given days 1 and 8. Treatment was repeated on day 2. Results: 28 patients (pts) were included. All patients were assessable for response and toxicity. Average age was 64 years, male/female ratio 20/8. Fourteen pts had liver metastases, 5 had lung and 9 had abdominal metastases. Median No of cycles was 4. Grade III and IV diarrhea was observed in 12 (44%) pts, vomiting in 9 (31%) pts, fatigue in 12 (44%) pts, grade IV leucopenia in 5 (17%) pts. Complete response was achieved in 3 (11%) pts, partial response in 15 (53%), stabilization of disease in 5 (18%) and tumor progression in 5 (18%) pts. Progression free survival is 8.4 months. Overall survival is not yet available. Conclusions: This regimen appears feasible with acceptable toxicity except for grade III diarrhea, on an outpatient treatment basis, with significant antitumor activity, without the requirement for indwelling catheters. It is also feasible for older patients.

No significant financial relationships to disclose.
Capecitabine and oxaliplatin as first-line chemotherapy in patients with metastatic colorectal carcinoma
Authors: Gennatas C. , Michalaki V. , Gennatas S. , Kondi-Paphiti A. , Voros D. , Smyrniotis V.
Published: March 2020

13578

Background: Capecitabine is an oral fluoropyrimidine with superior activity and safety compared with bolus 5-FU/LV in metastatic colorectal cancer (CRC). The aim of this study was to evaluate the efficacy and safety of a combination of capecitabine and oxaliplatin as first-line chemotherapy in patients with advanced CRC. Methods: Fourty-six patients (26 men and 20 women) with metastatic CRC entered this study. All patients were treated with capecitabine (1,000mg/m2 p.o.twice daily, days 1–14) and oxaliplatin (130mg/m2 on day 1). Cycles were repeated every 21 days until disease progression or unacceptable toxicity. Baseline characteristics: Median age 61 years (range 32–74), main sites of metastasis: Liver 32 patients (70%), liver and lungs 4 patients (9%), lungs 3 patients (6%), other sites 7 patients (15%). Results: 2 patients (4%) achieved complete response (CR), 17 patients (37%) achieved partial response (PR) and 7 patients (15%) attained stable disease (SD). With a median follow-up of 22 months the progression free survival was 7.5 months and overall survival was 19.0 months. All patients were assessable for toxicities. The most commonly encountered adverse events were from the gastrointestinal system (all grades 48%, grade 3, 6%). Neither toxic death nor life-threatening febrile neutropenia were reported. Conclusions: The combination of capecitabine and oxaliplatin is a convenient regimen in patients with advanced CRC that is associated with considerable efficacy and limited toxicity.

No significant financial relationships to disclose.
Outpatient chemotherapy with gemcitabine and oxaliplatin in advanced biliary tract cancer; a phase II study
Authors: Harder J. , Riecken B. , Kummer O. , Lohrmann C. , Geissler M. , Otto F. , Opitz O. , Henss H.
Published: March 2020

14006

Background: Biliary tract cancer is a heterogeneous tumor entity with a poor prognosis if unresectable. There is a need for an effective, safe and patient friendly treatment. Methods: Patients with typical histology for cholangiocarcinoma, adequate haematological, renal and liver function, measurable tumor formation, life expectancy for more than 3 months, and written informed consent were treated with Gemcitabine 1000mg/m2 (30 min infusion) day 1, 8, 15 and Oxaliplatin 100mg/m2 (2 h infusion) day 1 and 15. Chemotherapy cycles were repeated every 28 days (GEMOX-3 protocol). The data were collected according to the Simon 2-step design for a single centre phase II study (α=0.05; β=0.2). Planned sample size 29. Primary endpoint was the response rate; secondary endpoints were time to progression, median survival and safety profile. Results: Thirty-one consecutive patients were enrolled between July 2002 and April 2005. The efficacy was as follows: partial response 8 pts (26%), stable disease 14 pts (45%). Thus, the disease control rate was 71%, while 9 pts (29%) had progressive disease. Median time to progression was 6.5 months. Median overall survival after start of treatment was 10.4 months, after initial diagnosis it was 15.6 months. National Cancer Institute Common Toxicity Criteria grade 3–4 toxicities were transient thrombocytopenia in 23% of patients, peripheral sensory neuropathy 19%, leukopenia 16% and anaemia 10%. Conclusion: The GEMOX-3 protocol is active and well tolerated in patients with advanced biliary tract cancer. It can be applied in an outpatient setting with three treatments per month only. The positive results of this and other phase II trials underscore the importance of a large controlled clinical trial to verify the data.

No significant financial relationships to disclose.
Phase II trial of induction GEMOX followed by a twice-weekly infusion of gemcitabine and concurrent external beam radiation for the treatment of locally advanced pancreatic cancer
Authors: Leone F. , Sperti E. , Aliberti S. , Gatti M. , Massucco P. , Magnino A. , Faggiuolo R. , Gabriele P. , Capussotti L. , Aglietta M.
Published: March 2020

14019

Background: Combined chemo-radiation therapy may render curative resection feasible in pancreatic cancer deemed unresectable for vascular invasion. We previously demonstrated that primary radiotherapy with concurrent gemcitabine is feasible and allows clinical benefit. However, the percentage of resected patients was low. Methods: Patients with locally advanced pancreatic adenocarcinoma, received induction with 4 cycle GEMOX (gemcitabine 1000 mg/mq, day 1 and oxaliplatin 100 mg/mq, day 2) each 2-week cycle. Patients without disease progression received gemcitabine twice weekly (50 mg/mq/day) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy over 5.5 weeks) and were re-evaluated for resectability. Results: From 7/2003 to 11/2005, 20 patients entered this study, of whom 17 are evaluable for toxicity and 15 for treatment response. Twelve men and 8 women (median age 63 years; range 43–71) received a median of 3.5 cycles GEMOX (range 2–4). Fourteen patients completed the treatment with external beam radiation and received a median of 7 cycles with gemcitabine (range 3–10). In two patients chemotherapy during radiotherapy was omitted for previous toxicity, and one stopped also radiotherapy for gastrointestinal toxicity. No grade IV toxicities or deaths due to therapy were observed. Gastrointestinal grade III toxicities were observed in 3/17 patients (17.6%) after GEMOX and 6/16 patients (37.5%) during radiotherapy. Grades III hematologic toxicity and fatigue occurred in 4/16 (25%) and 2/16 (12.5%) respectively during radiotherapy. A disease control was obtained in 10/15 evaluable patients. One patient progressed after GEMOX and 4 after chemoradiotherapy. Eight patients (53%) appeared to be resectable: 1 patient is planned for surgery, 2 patients were found unresectable at lapaproscopy for peritoneal carcinomatosis or local extension; 5 patients underwent resection and in 4 of them (26%) margins were negative. Conclusions: Induction GEMOX followed by twice-weekly gemcitabine and upper abdominal radiation is feasible in patients with locally advanced pancreatic cancer and seems to induce a high resectability rate. This protocol warrants further evaluation.

No significant financial relationships to disclose.
A phase I study of capecitabine (CAP), carboplatin (CARB), paclitaxel (TAX) and external beam radiation therapy (EBRT) for patients with esophageal carcinoma (EC)
Authors: Kelsey C. R. , Czito B. G. , Bendell J. C. , Willett C. G. , Morse M. A. , D’Amico T. A. , Honeycutt W. , Franklin A. , Yu D. , Hurwitz H. I.
Published: March 2020

14044

Background: Chemoradiotherapy is used to treat esophageal cancer with curative intent or local symptom control. A phase I study of 5-FU + CARB + TAX + EBRT showed 100% RR and 50% pCR rate. CAP allows for fluoropyrimidine treatment without the inconvenience of an infusion pump. CARB allows for platinum treatment with less toxicity than cisplatin. We evaluated this combination of agents in a phase I study. Methods: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus requiring local therapy received CAP (825 mg/m2 bid on radiation days) + CARB (AUC 2 qweek) + TAX (60 mg/m2 qweek) + EBRT (1.8 Gy qd to 50.4 Gy). DLT was defined as any grade 4 heme toxicity, grade 3 heme toxicity lasting ≥ 7 days, ≥ grade 3 N/V, diarrhea, or esophagitis lasting ≥ 4 days despite optimal medical management, grade 3 other toxicity, inability to deliver 75% of scheduled CAP dose, or treatment delay > 3 days. Results: 13 pts were enrolled (10M, 3F). Median age was 62 (R- 48–78). EUS stage was uT3N0 (n=1), uT2N1 (n=1), or T3N1 (n=11). 2/3 pts had DLT at dose level 1 (both grade 4 esophagitis). Esophagectomy was performed in 2/3 patients, both pCR. Three pts were then enrolled at dose level -1 (CAP 600 mg/m2 bid + CARB AUC 1.5 + TAX 45 mg/m2). One patient developed DLT (grade 3 esophagitis) so 7 more pts were added at this dose level. Overall, 3/10 patients at dose level -1 developed DLT (two grade 3 esophagitis, one grade 3 hypotension). Esophagectomy was performed in 6/10 pts - 2/6 had pCR; 6/6 had pathologic downstaging. Conclusions: MTD for this regimen was CAP 625 mg/m2 bid + CARB AUC 1.5 + TAX 45 mg/m2 with EBRT to 50.4 Gy. However, at the MTD, this regimen is relatively toxic with no significant improvement in rate of pCR.

[Table: see text]
Phase 1 study of intra-arterial hepatic (IAH) delivery of doxorubicin-transdrug (DT) for patients with advanced hepatocellular carcinoma (HCC)
Authors: Merle P. , Si Ahmed S. , Habersetzer F. , Abergel A. , Taieb J. , Bonyhay L. , Costantini D. , Dufour-Lamartinie J. , Trepo C.
Published: March 2020

14094

Background: HCC is a highly chemoresistant due to MDR efflux pumps. DT is a newly cytotoxic chemotherapy composed of doxorubicin-loadded polyisohexylcyanoacrylate nanoparticles, allowing doxorubicin to overcome MDR pumps [Barraud, J Hepatol 2005; 42: 736]. Methods: 16 cirrhotic patients (pts) of Child-Pugh A with advanced HCC, transaminases/GGT <5N, platelets >100000/mm3, neutrophiles >1500/mm3, were enrolled in a multicentric noncontrolled study. A single IAH injection of 10, 20, 30, 35, or 40mg/m2 DT (respectively 3,3,4, and 3 pts) was performed, tolerance and efficacy being assessed 4 weeks later. Results: Grade 4 neutropenia (2pts at 40mg/m2) gave the Maximal Tolerated Dose. Grade 2–3 hypertransaminasemia (transient) occurred dose-independently. Two serious adverse events (SAE) were hypotension and acute respiratory distress syndrome. All adverse events (AE) (90% grade 1–2) occurring during injection were dose-independent, and completely and fastly recovered : cough (6pts), dyspnea (2pts), SaO2 decrease (2pts), tachycardia (2pts), bradycardia (2pts), hypotension (2pts). Anti-tumor efficacy of DT was evaluated by helicoidal CT-scan with contrast injection 4 weeks after injection : 3pts (20%) showed partial response with frank decrease of contrast enhancement at arterial perfusion, 8pts (50%) remained stable, and 5pts (30%) had progression. Conclusions: This phase 1 showed that a single IAH injection of DT was safe until 35 mg/m2 for Child-Pugh A patients with advanced HCC. This dosage will be retained for the phase 2 step comprising 3 injections at 4-week intervals which will aim at confirming the antitumour efficacy of DT for HCC.

[Table: see text]
The advantages of circular stapling instrument compared with Albert-Lembert suture for anastomosis of Billroth I gastrectomy for gastric cancer
Authors: Imamura H. , Furukawa H. , Tatsuta M. , Kishimoto T. , Yamamoto K. , Yamamoto K. , Ohshiro R.
Published: March 2020

14104

Background: In Japan, reconstruction with Billroth I using Albert-Lembert suture had been usually performed in distal gastrectomy for gastric cancer. However stapling instruments have within recent years gained wide acceptance not only in total gastrectomy but also in distal gastrectomy. We have introduced circular stapling instrument for anastomosis reconstructed with Billroth I since June 2001. Methods: 111 and 222 patients with gastric cancer underwent distal gastrectomy reconstructed with Billroth I using Albert-Lembert suture from June 1999 to May 2001 (Group A) and using circular stapling instrument from June 2001 to December 2003 (Group B) for anastmosis in our institute, respectively. Albert-Lembert suture was performed as end-to-end gastroduodenostomy followed by resection of proximal line stapled across with liner cutter instrument. The procedure of anastomosis using circular stapling instrument was as followed; the distal duodenum was clamped with the purse-string instrument, divided proximally, the anvil was attached, the purse-string was tied down, the circular stapler without anvil was inserted through a gastrotomy, brought out through a stab wound at the anastomosis site, the instrument was closed and fired, and gastrectomy involving the site of gastrotomy was closed with linear cutter instrument. The followed-up periods of all patients from surgery were more than 2 years. We retrospectively compared the incidence of anastomosis-related complications within 2 years from surgery consisting of anastomotic bleeding, leakage, and stenosis. P-values were calculated statistically using χ2-test. Results: Anastomotic bleeding occurred in 1 (0.45%) patient of Group B, but in none of Group A (P=0.48). Anastomotic leakage occurred in 2 patients (1.80%) of Group A, but in none of Group B (P=0.045). Anastomotic stenosis occurred in 2 patients (0.90%) of Group B, but in none of Group A (P=0.32). All complications were recovered and all patients left hospital in the safety. Conclusions: Our data indicated that circular stapling instrument for anastomosis of Billroth I gastrectomy for gastric cancer significantly reduced the incidence of anastomotic leakage compared with Albert-Lembert suture.

No significant financial relationships to disclose.
A phase II trial of capecitabine and docetaxel in patients with previously treated pancreatic cancer
Authors: Lopes G. , Bastos B. , Ahn E. , Quesada J. A. , Allison M. , Flores A. , Ribeiro A. , Levi J. , Macintyre J. , Rocha-Lima C. M.
Published: March 2020

14111

Background: There is no accepted standard treatment for patients with advanced pancreatic cancer who progress after gemcitabine-based therapy. Capecitabine and docetaxel have single-agent activity in pancreatic cancer and have documented synergy in both pre-clinical models and in the treatment of other solid tumors. Methods: A phase II trial with a 3-stage sequential design was planned to assess the efficacy (primary end-point: response rate) and toxicity of capecitabine 800 mg/m2 PO bid on days 1–14 in combination with docetaxel 30 mg/m2 IV on days 1 and 8 of each 21-day cycle in patients with advanced pancreatic cancer who failed first-line gemcitabine-based chemotherapy. If no responses are observed after 13 patients or less than 3 responses are seen after 26 patients, accrual will stop and the combination deemed ineffective. Results: Eight patients have been enrolled (5 women, 3 men). Median age was 67 years. ECOG PS was as follows: PS 1, three patients; PS 2, five patients. All patients had adequate organ function. A total of 26 cycles have been administered (median: 2 cycles, range 1 to 8). Four patients had stable disease (median duration 9 weeks, range 6 to 24), and 3 had progressed at the time of first evaluation (2 cycles). One patient has not yet completed 2 cycles and is therefore not assessable for radiologic response. Out of 7 patients with an elevated CA 19–9, four had a decrease of 50% or greater while on chemotherapy. Grade 1 or 2 toxicity was seen in 3 patients (diarrhea, 1 patient; fatigue, 2 patients). Grade 3 or 4 toxicity was as follows: fatigue, 2 patients; dehydration, 1 patient; neuropathy, 1 patient. There were no treatment related deaths. Enrollment continues. Efficacy data fulfilling the first stage sequential design should be available at the time of the meeting. Median survival for all patients is currently 13 weeks (range 7–23 weeks) Conclusions: Capecitabine in combination with docetaxel is a well-tolerated regimen in the treatment of patients with pancreatic cancer who have failed prior gemcitabine-based therapy. Four out of 8 patients have had stable disease. Four of 7 patients have had a decrease of 50% or greater in CA 19.9 levels. Enrollment continues. Median survival of 13 weeks underscores the poor prognosis of this patient population.

[Table: see text]
A multicenter phase 2 consortium (P2C) study of triapine in patients (pts) with advanced adenocarcinoma of the pancreas
Authors: Groteluschen D. L. , Mahoney M. R. , Pitot H. C. , Laheru D. , Kolesar J. , Thomas J. P. , Erlichman C. , Holen K. D.
Published: March 2020

14118

Background: Triapine is a small molecule iron chelator that has been shown to inhibit ribonucleotide reductase (RR) at the M2 subunit. Early trials suggested activity in pancreatic cancer. The P2C initiated a study of single agent Triapine as both first-line therapy and for pts with gemcitabine-refractory disease. Correlatives included: pharmacokinetics, MDR polymorphisms, and the effects of Triapine on cell cycle and electron paramagnetic resonance spectroscopy (EPR). Methods: Standard eligibility criteria were used, however, pts with G6PD deficiency were excluded. Triapine was given 96 mg/m2 IV over 2 hours, days 1–4 and 15–18, repeated q 28 days. Primary goals - evaluate survival (S) at 6 mos (previously untreated pts) and 4 mos (refractory pts). Interim analyses were planned when 28 previously untreated and 20 refractory pts were enrolled. Results: 14 eligible pts were enrolled in 10 mos (13 refractory, 9 male). The previously untreated pt received only 1 cycle secondary to progressive disease. Of the 13 refractory pts, 7 pts received at most 2 cycles; 6 received 1. Disease progression precluded further treatment in 11 pts. 6 pts had Gr 4 toxicities at least possibly related to drug, including: neutropenia-4, hyperkalemia-1, hyponatremia-1, leukopenia-1, thrombocytopenia-1, hypophosphatemia-1. 6 pts had a Gr 3 fatigue. One refractory patient expired on study. No responses were seen. Estimated 4 mos S in refractory pts is 16% (95% CI 3–94). EPR studies showed that Triapine led to a loss of the RR tyrosine radical EPR signal. Conclusions: Enrollment was suspended due to excess toxicity and lack of activity in pts refractory to gemcitabine. Correlative studies confirm the mechanism of action of Triapine as a chelating agent on RR. Supported by NCI Grant N01 CM17104 and the NCI Translational Research Fund.

No significant financial relationships to disclose.
Concomitant chemoradiotherapy with orally used agents in locally advanced gastric carcinoma: Two years results
Authors: Akboru M. H. , Dincer S. T. , Yoney A. , Askaroglu B. , Unsal M.
Published: March 2020

14127

Background: We designed a prospective study to evaluate tolerability, toxicity and effectiveness of concomitant chemoradiotherapy with oral tegafur-uracil (UFT) and leucovorin in locally advanced gastric carcinoma. 13 patients admitted to our center in 10 months of 2003 (March– December) were included. Methods: Only one of the patients was female (7.7%). Median age was 52 (34–72). All of them were operated with negative surgical margins (53.8% of them have undergone total gastrectomy and rest of them were operated subtotally). All of them have 0 and 1 performance status (ECOG). Their tumor were mostly located in antrum (53.8%). 4 (30.8%) of them in stage II and in stage IIIA, IIIB and IV were as follows: 2 (15.4%), 5 (38.5%) and 2 (15.4%). Median lymph node dissection was 14 (7–31). Median time interval between surgery and treatment was 49 days (25–63). All patients were treated 45 Gy (one patient 39.6 Gy and other patient 50.4 Gy) locoregional radiotherapy (RT) and UFT 300 mg/m2/day + leucovorin 90 mg/day in three times a day during RT. Results: All patients tolerated therapy well (RT was interrupted 3 times just in one patient because of grade III emesis). At the end of median two years follow up; recurrence was seen as metastasis in 4 (30.8%) patients and locoregional in 3 (23.1%). 8 patients (61.5%) died (one of them was not related). Median progression free survival was 17 months (6–34) with 53.8% in one year and 38.5% in two years. Median overall survival (OS) was 24 months (8–34), one and two years OS were 76.9% and 46.2%, respectively. Conclusions: Concomitant chemoradiotherapy with orally used agent (UFT and leucovorin) in locally advanced gastric carcinoma is well tolerated regimen. But to increase survival data by continuing therapy with these agent after chemoradiotherapy must be researched. To answer this question another study was conducted and is going on in our center.

No significant financial relationships to disclose.
Outcome of advanced gastric cancer patients with disseminated intravascular coagulation and bone marrow metastasis is improved by weekly 24-Hour infusional high-dose 5-fluorouracil and leucovorin (HDFL)-based chemotherapy
Authors: Huang T. , Hsu C. , Cheng A. , Yeh K.
Published: March 2020

14132

Background: Advanced gastric cancer (AGC) patients manifesting with acute disseminated intravascular coagulation (DIC) and diffuse bone marrow metastasis have inevitably led a fatal outcome within a median of 2–4 weeks. We previously reported that weekly 24-hour infusional high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (HDFL: 5-FU of 2,000–2,600 mg/m2/wk and LV 300 mg/m2/wk) chemotherapy with negligible myelosuppression has been successfully used in the treatment of these patients (Yeh KH & Cheng AL, Br J Haematol 1998;100:769–72). The study planned to determine the treatment outcome in a larger group of this disease entity being treated with HDFL-based chemotherapy. Methods: This is a retrospective study. Bone marrow study is routinely done for gastric cancer patients with DIC in our institute. We searched for gastric cancer patients with DIC or bone marrow metastasis from 1994 to 2005. Results: A total of 21 AGC patients (M: 13, F: 8) who had unequivocal evidence of DIC or biopsy-proven bone marrow metastasis have been diagnosed at National Taiwan University Hospital between 1994 and 2005. At initial presentations, 18 patients had evident laboratory findings of DIC. Nine of them had symptomatic DIC and 8 patients had significant thrombocytopenia (< 50,000/mm3). All patients received HDFL-based chemotherapy as the initial treatment. Seventeen of them showed significant improvement in both clinical symptoms and laboratory abnormalities of DIC. The median overall survival (OS) of the whole group of patients since the diagnosis of DIC or bone marrow metastasis was 7 months (range: 1 week–3 years). Conclusions: Manifestations with acute DIC and bone marrow metastasis in AGC patients constitute a rare disease entity with a grave prognosis. Before introduction of HDFL for the treatment of AGC at our institute, this group of patients was extremely difficult to treat, and usually died within 2–4 weeks. Current analysis revealed that OS of this group of patients has been improved up to a median of 7 months, suggesting a significant improvement in the treatment outcome.

No significant financial relationships to disclose.
Docetaxel, 5-fluorouracil and nedaplatin as second-line chemotherapy for patients with esophageal cancer after esophagectomy: A pilot study
Authors: Mafune K. , Yamada K. , Imamura K. , Kubota K. , Kaminishi M.
Published: March 2020

14140

Background: We investigated the combination of docetaxel, 5-fluorouracil (5FU) and cisplatin analog, nedaplatin (CDGP) as second-line chemotherapy after esophagectomy. Methods: Eight patients with recurrent esophageal cancer who had undergone adjuvant 5FU/cisplatin after esophagectomy were included this study (7 male, 1 female; median ECOG performance status: 1). Histologic type of all esophageal cancer was squamous cell carcinoma. Patients received docetaxel 60 mg/m2 on day 1, 5FU 600 mg/m2 on days 1–5, and CDGP60 mg/m2 on day 4 every 3 weeks. A total of 17 chemotherapy cycles was administered. The median number of cycles was 2 (range 1–5). Results: The overall response rate was 62.5%. The median overall survival was 42 weeks, and the median progression-free survival was 26 weeks. Hematological and non-hematological toxicities were moderate (neutropenia WHO grade III/IV: 62.5%, alopecia grade II/III: 75%, nausea/vomiting grade II/III: 50%, neurotoxicity grade II: 12.5%). Conclusions: The combination of docetaxel, 5FU and CDGP is an active regimen with moderate toxicity in the treatment of patients with recurrent esophageal cancer. This pilot study suggests the feasibility of a combination treatment containing a taxan, 5FU and cisplatin or its analog in esophageal squmaous cell carcinoma.

No significant financial relationships to disclose.
Outcomes of hepatocellular carcinoma
Authors: Yildirim Y. , Ozyilkan O. , Akcali Z. , Remzi E. , Sevmis S. , Demirhan B. , Bilezikci B. , Karakayali H. , Haberal M.
Published: March 2020

14141

Background: Hepatocelluler carcinoma (HCC) related mortality remains high although recent advances in management in cancer therapy. Treatment options of HCC can be surgical resection, percutaneus alcohol injection (PAI), transcatheter arterial embolisation (TAE), radiofrequency ablation (RF), systemic chemotherapy or liver transplantation. However it is unclear how effective are these methods for treating HCC. Methods: We reviewed the treatment results of 56 patients diagnosed with HCC between 1996–2005. Local treatment (PAI or TAE) or systemic chemotherapy or curative surgery (resection or liver transplantation) or no therapy was applied. Our inclusion criteria for transplantation were (independent of tumor size and number of tumor nodules) no invasion of major vascular structures and no extrahepatic disease, negative surgical exploration including hilar lymph node frozen section. Kaplan-Meier survival analyses were used to evaluate outcome. Results: Median age at diagnosis was 57 years (range: 18–90). Of 56 patients 20 (35.7%) are alive, 14 (25%) are loss the follow-up and 22 (39.3%) are died. Sixty-eight percent of patients received therapy, and 32% received no specific therapy. Among patients who received therapy transplantation was the most common procedure (n: 18 patients, 47.4%). Three patients underwent surgery (70.9%); local therapies were applied 13 patients (34.2%). Twenty-three (46.4%) patients have single lesion in the liver, 27 (48.9%) patients have multiple lesions. No statistical difference was found in survival of patients with single lesion or multiple lesions (p > 0.05). Median follow-up of patients is 9 months (range: 1–41 months). Patients who underwent surgery or liver transplantation have statistically significant longer survival than patients treated with local therapies (PAI or TAE) (p < 0.01). Conclusion: HCC is a chemoresistant tumor. None of the used chemotherapy regimen demonstrated marked benefit in survival. Complete surgical excision can be curative but only small percentage of HCCs are resectable at the time of diagnosis. However liver transplantation in selected patients can cure both HCC and underlying cirrhosis. Expanded criteria for liver transplantation in our clinic seems to be beneficial on this disease.

No significant financial relationships to disclose.
Low dose mitomycin c, capecitabine & radiation for HIV patients with anal squamous cell carcinoma
Authors: Wadleigh R. , Dinh K. , Manning J. , Kuntz A. , Dorn R.
Published: March 2020

14148

Background: Chemoradiotherapy has replaced radical surgery as the initial treatment of choice for anal squamous cell carcinoma (ASCC). Optimal chemotherapy regimen for ASCC in HIV positive patients is not yet defined. The addition of mitomycin C to 5-FU and radiotherapy in the past improves local control, colostomy-free, and even disease-free survival in large tumors. The concern is hematologic toxicity if use in HIV positive patients. We report 2 cases safely using low dose mitomycin C, capecitabine and concurrent XRT. One of these patients has ESRD, which the use of cisplatin is not an option. Methods: 2 HIV positive patients, (CD4 range 106–113, at diagnosis of ASCC) were treated with low dose of mitomycin C on day 1 for 2 cycles (5mg flat dose), day 1–7 capecitabine titrated up to 1.5 gm/m2 divided b.i.d, and concurrent XRT (total dose 5040 cGy). Prior to treatment, 1 patient was diagnosed with squamous cell carcinoma in-situ and the other with stage 1 squamous cell carcinoma. 1 patient has end stage renal disease with SCr between 10 and 12 mg/dl at the time of treatment. Results: Both patients completed treatment. No grade 3 or 4 hematologic or gastrointestinal toxicities were noted. No hand-foot syndrome was observed probably due to low dose of capecitabine. Both patients are still alive and remain in remission (16–18 months post treatment). Conclusions: Our 2 cases suggest that the use of low dose mitomycin C in addition to capecitabine and XRT is well tolerated and is efficacious in HIV-positive patients with ASCC.

No significant financial relationships to disclose.
Oxaliplatin, 5-fluorouracil, and folinic acid as first-line chemotherapy for elderly patients with advanced gastric cancer
Authors: Choi I. , Lee K. , Oh D. , Kim J. , Lee S. , Kim D. , Im S. , Kim T. , Heo D. , Bang Y.
Published: March 2020

14155

Background: We investigated the efficacy and safety of an oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) as first-line chemotherapy for elderly patients with advanced gastric cancer. Methods: Chemotherapy-naïve patients (≥65 yr of age) with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Chemotherapy consisted of oxaliplatin 100 mg/m2 and FA 100 mg/m2 (2-hour intravenous infusion), then 5-FU 2400 mg/m2 (46-hour continuous infusion) every 14 days. Results: A total of 24 patients were enrolled between September 2003 and July 2005. Of 22 evaluable patients, none achieved complete response (CR) and 11 achieved partial response (PR), resulting in an overall response rate of 50%. Median progression-free survival (PFS) was 5.4 months (95% CI: 5.1–5.8 months) and median overall survival (OS) was 7.4 months (95% CI: 4.4–10.4 months). The main toxicities were anemia and leucopenia, which were observed in 39.8% and 19.0%, respectively, of the total cycles administered. There were 2 cycles of grade 4 leucopenia and febrile neutropenia was not observed. Conclusions: This oxaliplatin/5-FU/FA regimen shows good efficacy and an acceptable toxicity profile in elderly patients with advanced gastric cancer.

No significant financial relationships to disclose.
A phase II trial of gemcitabine and docetaxel in hormone-refractory metastatic prostate cancer
Authors: Thakkar S. , Hutson T. , Garcia J. , Rothaermal J. , Bart M. , Dreicer R.
Published: March 2020

14501

Background: Docetaxel is a microtubule stabilizing agent with demonstrated ability to improve survival in patients (pts) with hormone refractory metastatic prostate cancer (HRMPC). Gemcitabine is a nucleoside analogue that exhibits broad antitumor activity, although as a single agent has modest activity in advanced prostate cancer. The combination of docetaxel and gemcitabine has demonstrated significant activity in a variety of chemotherapy resistant neoplasms. We performed a phase II study of this combination to assess its safety and antitumor activity in chemotherapy naïve patients with HRMPC. Methods: Eligible pts had HRMPC with radiologic and/or biochemical evidence of progression following antiandrogen withdrawal with castrate testosterone levels, ECOG PS 0–2 and adequate organ function; no prior chemotherapy was permitted. Gemcitabine (800 mg/m2) was administered on days 1 and 8 and docetaxel (75mg/m2) on day 8 every 21 days for a maximum of 6 cycles. Results: Twenty-nine pts have been enrolled to date with 22 currently evaluable for response, all are evaluable for toxicity. The median age was 68. The average number of cycles completed was 4.9. Nine pts have experienced grade 4 neutropenia (1 neutropenic fever admission). Twelve of 29 pts have required dose delays secondary to wbc or platelets, two pts have required dose modification. Non-hematologic grade 3/4 toxicities include 1 pt with a PE, 1 grade 4 dyspnea, 1 grade 4 GI bleed. Four pts (18%) achieved measurable disease + PSA, partial response (PR), 7 (32%) additional pts had >50% decline in PSA, for a composite overall response rate of 50%. Conclusions: The combination of gemcitabine and docetaxel is moderately toxic primarily impacting bone marrow reserve. Although there is evidence of significant antitumor activity, the ulitmiate utility of this doublet remains undefined. Accrual to this study is ongoing.

[Table: see text]
Safety and efficacy of intravesical bacillus Calmette-Guérin instillations in steroid-treated and immunocompromised patients
Authors: Yossepowitch O. , Eggener S. E. , Bochner B. H. , Donat S. M. , Herr H. W. , Dalbagni G.
Published: March 2020

14507

Background: We assess the safety and efficacy of intravesical bacillus Calmette-Guérin (BCG) for high-risk superficial bladder cancer in steroid-treated and immunocompromised patients. Methods: We retrospectively reviewed charts of 697 patients treated with BCG instillations from 1991 to 2004. In 24 patients (3.5%), either an underlying comorbidity directly affecting the immune system was diagnosed before BCG administration, or steroids were administered at least 6 weeks before and at the time of BCG instillations. The immunosuppressive effect of the steroids was assessed by percentage of lymphocytes. End-points were BCG response at 6 months (defined as normal cystoscopy, cytology, and biopsy when available) and treatment-related toxicity. Results: Four patients (17%) had an active lymphoma or chronic lymphocytic leukemia during administration of BCG, and 21 (88%) had a concurrent condition for which oral steroids (11 patients), inhaled steroids (14 patients), or both (4 patients) were administered. Patients treated with oral steroids had a lower percentage of lymphocytes (12.3%) compared to patients treated with inhaled steroids (17.5%) or 15 age-matched patients with high-risk superficial bladder cancer and no steroid treatment (18.6%). The overall BCG response rate at 6 months was 58%. Of the 24 patients, 10 had disease recurrence and 3 had disease progression at a median follow-up of 63.5 months (IQR 19.5, 89). One patient treated with oral steroids developed a self-limited febrile disease and worsening of myalgia 48 hours after his third BCG cycle. No other systemic adverse event following BCG therapy was recorded, and all patients completed their scheduled treatments. Conclusions: Intravesical BCG is a viable therapeutic option for patients with high-risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low-dose oral steroids, or treatment with inhaled steroids. The BCG response rate at 6 months and the side effects profile associated with BCG therapy in these patients are comparable to patients with no evidence of immunosuppression. Further studies are warranted to assess the safety and efficacy of BCG instillations in critically immunocompromised patients.

No significant financial relationships to disclose.
Randomized phase II trial of irofulven (IROF)/prednisone (P), IROF/capecitabine (C)/P or mitoxantrone (M)/P in docetaxel-pretreated hormone refractory prostate cancer (HRPC) patients (pts)
Authors: Hart L. , Ciuleanu T. , Hainsworth J. , Oudard S. , Berger E. R. , Alexandre J. , Chi K. N. , Ruether D. , MacDonald J. R. , Cvitkovic E.
Published: March 2020

14513

Background: IROF, a semisynthetic derivative of the natural product illudin S, is a novel DNA binding agent. IROF alone or in combination has shown activity in phase I-II trials in HRPC, notably with IROF/C (Cvitkovic et al, ASCO 2004). Methods: Pts with histologically-proven metastatic HRPC who progressed (RECIST or PSA) during prior docetaxel or within 3 months of discontinuing treatment, with adequate hematologic and organ functions and KPS ≥70% were stratified by pain and randomized to one of three treatments: Arm A: IROF (0.45 mg/kg, day 1 and 8 q3weeks [w]) and P (10 mg po daily); Arm B: IROF (0.4 mg/kg day 1 and 15), C(2000 mg/m2 day 1–15 q4w) and P; or Arm C: M (12 mg/m2 q3w) and P. Primary endpoint was TTP (RECIST, PSA or clinical progression); secondary endpoints included PSA response (≥50% decrease for ≥4 w), pain response, and toxicity; 135 pts are planned in a 2:2:1 ratio. The study was powered to detect a difference in TTP of 1.5 vs 3 months. Results: As of Dec 2005, 78 pts were randomized and treated with ≥ 5 months follow-up (A/B/C: 31/31/16). Median age (A/B/C) 69/70/61, KPS ≥80% 24/28/9, median baseline PSA ng/mL 90/147/235, disease related pain at baseline 61%/58%/63%; other characteristics, including metastatic site distribution, were similar between arms. Safety: 65 pts were evaluated for safety. Median cycles/Pt (A, B, C) 3/2/2; grade 3/4 toxicities (% pts A, B, C): asthenia (4%, 16%, 0%), vomiting (0%, 12%, 0%) and diarrhea (4%, 8%, 0%). The most common grade 3/4 laboratory abnormalities were neutropenia (10%, 6%, 31%) and thrombocytopenia (15%, 12%, 0%). Conclusion: IROF in combination with P and, in particular, C/P shows improved activity and acceptable tolerance compared to M/P in docetaxel-resistant HRPC. Patient accrual is complete as of Jan 2006, and final results will be presented. [Table: see text]

[Table: see text]
Cellular localization of thrombin in prostate: Implications for thrombin targeted therapy in prostate cancer
Authors: Kohli M. , Huang J. , Palapattu G. , Dennis R. , Yao J. , Lester T. , Ricke W.
Published: March 2020

14527

Background: Tumor and coagulation interaction is complex and heterogeneous. Expression of an intact repertoire of coagulation proteins is not detected in all tumor types. Thrombin, a key coagulation protein, which has been observed to promote tumorigenesis in experimental models, is not expressed on breast, colon and squamous lung cancer cells, but has been detected on small cell lung, melanoma and renal cancer epithelium. In prostate cancer, expression of its receptor, protease activated receptor-1 (PAR-1) has been previously reported but thrombin expression on epithelium not determined. Therefore, we evaluated thrombin and prothrombin expression in prostate specimens. Methods: Quantitative real-time PCR was performed for (pro)thrombin mRNA expression in fresh prostate cancer tissue lysates obtained from localized disease (n = 9 prostatectomy specimens) and advanced disease (n = 7 channel trans-urethral prostate resection specimens). Prothrombin and thrombin protein immunohistochemistry was performed on anonymized prostate tissue micro arrays which included benign (n = 117), prostate intra-epithelial neoplasia (PIN; n = 26) and prostate cancer (n = 112) cores. Results: (Pro)thrombin mRNA expression (normalized to 18s mRNA) was detected in all cancer tissue lysates. Mean intensity of expression in advanced cancer specimens was 20.3 compared to 14.0 for local stage specimens (p = 0.09; Wilcoxon rank sum test). Spatially, expression of thrombin was detected in stroma, benign and malignant epithelium (see Table) and on vascular endothelium. Prothrombin localization was similar to thrombin expression. Conclusions: Thrombin’s tumorigenic effects via PAR-1 activation provide novel therapeutic targets in tumors expressing thrombin-PAR1 axis. The current study confirms thrombin expression on prostate epithelium and taken with previous results of PAR1 epithelial expression, provides a rationale for exploring specific thrombin inhibitors and/or PAR inhibitors in prostate cancer. [Table: see text]

No significant financial relationships to disclose.