bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survey of cetuximab activity in irinotecan-refractory metastatic colorectal cancer patients
Authors: Afchain P. , Bachet J. B. , André T. , Landi B. , Mitry E. , Tournigand C. , Lepère C. , Louvet C. , Vaillant J. N. , Rougier P. 
Published: March 2020

13533 Background: The BOND study demonstrated Cetuximab (Cx) activity in irinotecan-refractory metastatic colorectal cancer (IRMCCR) patients (pts). Cx was approved in Europe early 2004 for this population. The aim of this study was to survey its efficacy in a unselected population of IRMCCR treated in 4 french academic centers. Methods: Data of all IRMCCR pts who had received Cx with or without irinotecan regimen between Jan 2004 and Sept 2005 were included in this survey. Exhaustivity of treated pts was established based on pharmacy registry. Primary end-point was time to tumor progression (TTP). Secondary end-points were overall survival (OS) and tumor response (RECIST). Results: Characteristics of the 76 included IRMCCR pts were : male/female : 44/32; median age 59.5 yrs (range 23 - 79); performance status : 0–1 (59 pts) and 2–3 (17); median number of tumor sites : 2 (1 - 5). The median number of chemotherapy regimens preceeding first Cx administration was 3 (range 1 to 5). At least one local treatment of the metastases (surgical resection and/or radiofrequency ablation) was a part of the strategy before Cx for 39 pts (51.3%). EGFR status was positive in 72 pts and negative in 4. Cx was administered : alone in 4 pts, combined with FOLFIRI in 4 and with irinotecan alone in 68 (89%). 10 pts received only one infusion Cx (early clinical progression : 6; patient decision : 2; early death : 2). Median number of Cx infusions was 10 (range 1 to 60). Median TTP (intent-to-treat) was 3.3 months [IC95% : 2.2–4.6]. Median OS since first-line chemotherapy and first Cx administration were 33.6 months [IC95% : 27.7–41.1] and 7.6 months [IC95% : 5.6–9.5], respectively. Tumor response (full population) was complete response 1.3%, partial response 19.7% (overall response 21%), stable disease 25% (disease control : 46%), progression 37% and not evaluable 17%. Conclusions: This therapeutic survey in a unselected population of IRMCCR are in accordance with the results of the BOND study for TTP, OS and tumor response. (supported by ADEBIOPHARM ER48). [Table: see text]
Tissue inhibitor of metalloproteinases 1 (TIMP-1) and tumor type M2 pyruvate kinase (TuM2-PK) were compared with established markers in advanced colorectal cancer
Authors: Siepmann S. , Pollmann D. , Geppert R. , Wernecke K. D. , Possinger K. , Lueftner D. 
Published: March 2020

13537 Background: Recently, a high expression of TIMP-1 was demonstrated by immunohistochemistry in colorectal cancer (CRC). TIMP-1 can also be detected in plasma of those patients (pts). We investigated the longitudinal concentrations of TIMP-1 in 37 pts with advanced CRC and correlated the monitoring performance of TIMP-1 to CEA and CA 19–9 as established markers of tumor load in CRC. In addition, the plasma level of TuM2-PK as novel marker of disease activity was integrated into the analysis. Methods: Plasma TIMP-1 (Bayer Diagnostics/Oncogene Science, Tarrytown/Boston, USA) and TuM2-PK (Schebo Biotech, Giessen, Germany) levels were measured using standardized ELISA assays while serum CEA and CA 19–9 were determined using chemiluminescence immunoassays (Bayer Diagnostics, Tarrytown/NY). The nonparametric analysis of variance for repeated measurements by Brunner was used to test for time effects between the selected 3 time points: 1. baseline at initiation of systemic chemotherapy for metastatic disease; 2: best response; 3: later progression. Results: We grouped 37 pts with regard to best response to chemotherapy as follows: complete or partial remission (CR/PR): n=10; stable disease (SD): n=21; primary progressive disease (PD): n=6. TIMP-1 and TuM2-PK concentrations increased significantly from baseline to progression (p<0.001 and p=0.003, respectively). The plasma levels of patients with objective response (CR/PR) dropped significantly for TuM2-PK (p=0.001) and TIMP-1 (p=0.001), while CA 19–9 and CEA did not change (p=0.94 and p=0.10, respectively). No significant change could be demonstrated in the SD group for TuM2-PK (p=0.26), TIMP-1 (p=0.69) and for CEA (p=0.25), whereas CA 19–9 concentrations decreased significantly (p=0.04). Conclusions: Innovative markers like TIMP-1 and TuM2-PK provided a much higher monitoring quality than established markers like CEA and CA 19–9 in advanced CRC. As the later cancer-associated proteins are recommended by internationally acknowledged guidelines, larger comparative trials are warranted asking the important question whether a replacement of CEA by one or a panel of new markers may provide additional clinical information. No significant financial relationships to disclose.
Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal carcinoma: Preliminary results
Authors: Salud A. , Alonso V. , Lambea J. , Valencia J. , Mira M. , Polo S. , Escudero P. , Sierra E. , Lao J. 
Published: March 2020

13543 Background: Preoperative chemoradiotherapy has shown to improve local control and sphincter preservation with decreased acute toxicity compared with postoperative treatment in locally advanced rectal carcinoma. The primary endpoint of this phase II trial was pathologic tumor response. Secondary endpoints were sphincter preservation and toxicity. Methods: Inclusion criteria: rectal adenocarcinoma <12 cms from anal verge, clinical stage T3–4 and/or N+, adequate renal, hematological and liver function. Planned sample for this trial was 43 patients. Treatment scheme: pelvic radiotherapy (50.4 Gy/28 fractions) and chemotherapy: Capecitabine 825 mg/m2/12 hours on days 1–5 + Oxaliplatin 50 mg/m2 on day 1 every week (weeks 1–6). Surgery with TME was performed between 6–8 weeks after the end of the treatment. Adjuvant chemotherapy was administered after surgery according each center criteria. Results: 37 patients have been recruited between February and December 2005. 26 male/11 female. Median age 70 years (range 38–79). Clinical stage (determined by EUS+CT or RMI): cT2 1p/cT3 33p/cT4 3p/cN+ 27p. Tumor location (from anal verge): ≤ 5 cm in 15p, >5 cm in 22p. Surgery (performed in 26 patients) consisted of low anterior resection in 13p and abdominal-perineal resection in 13p. Tumor downstaging was observed in 17p (65%), 20 (77%) had negative lymph nodes, including 6p with complete pathological response (23%) and four with only microfoci of tumor remaining (15%). Main adverse effects (NCI-CTC): diarrhea G3–4 19%, sensitive peripheral neurotoxicity G1 38%, skin G2 11%, nausea/vomiting G2 11%, fatigue/malaise G3 4%, neutropenia G3 7%. Conclusions: Preliminary results show that preoperative chemoradiotherapy with capecitabine and oxaliplatin is a well tolerated regimen for locally advanced operable rectal cancer leading to a high probability of tumor downstaging. No significant financial relationships to disclose.
BECAM: A salvage protocol with bevacizumab, capecitabin, and mitomycin C for patients with refractory metastatic colorectal cancer (CRC) or gastric cancer (GC)
Authors: Peinert S. , Arnold D. , Siewczynski R. , Kegel T. , Heider C. , Nietsch H. , Schmoll H. 
Published: March 2020

13554 Background: Bevacizumab (Bev), a monoclonal antibody targeted against VEGF, has shown to improve efficacy in CRC when combined with chemotherapy. Combination schedules of fluoropyrimidines with mitomycin C (MMC) are active in both CRC and GC. This study was to explore the combination of Bev with a previously reported schedule of Capecitabine (Cap) and MMC (BECAM) in heavily pretreated patients (pts) with GC or CRC. Methods: Pts had to be refractory to at least 3 treatment lines, incl. 5-FU, oxaliplatin, irinotecan, and cetuximab in CRC; 2 lines with 5-FU, platinum, irinotecan or taxane in GC. A treatment cycle consisted of a 1-hour-infusion of Bev 7.5 mg/kg d1, bolus MMC 7mg/m2 d1 and Cap 1000mg/m2 bid d1–14, all qd22. Toxicity was assessed every 3 weeks (wk) and tumor evaluation (CT/MRI) was done every 9 wk. Results: 19 pts were included: m/f 8/11; GC 4, CRC 15, age 63 yrs [42–76], Karnofsky PS 80% [70–100]. Median no. of preceding regimens was 3 [2–6]. A total of 87 cycles were given. Median no. of cycles per pt. was 3 [2–15]. 18 pts were evaluable for toxicity (WHO scale) and efficacy: Grade 3/4 toxicities were thrombocytopenia (5/0), hypertension (1/0), and hemorrhage (0/1). The latter caused cessation of further administration of Bev. Gastrointestinal and other hematologic toxicities did not exceed grade 2. Response: PR was seen in 3 pts (16%; 1/4 GC, 2/14 CRC), stable disease for > 9 wk in 5 pts (1 GC, 4 CRC), leading to a tumor control rate of 44%. Median progression free and overall survival were 3.0 [2–11] and 5.0 [2.5–13] months. However, duration of objective response was remarkable in lasting 7.4–10.0 months. Conclusions: BECAM shows considerable activity in this group of heavily pretreated pts with CRC or GC. Toxicity was generally mild except for MMC-induced thrombocytopenia and (probably) Bev-induced bleeding (gastric tumor site). Despite previous reports of limited activity with Bev/5-FU in refractory pts (NCI TRC trial), BECAM is able to induce long lasting objective responses and therefore merits further investigation in both tumor types. [Table: see text]
Phase II study of fixed dose rate gemcitabine in patients with pretreated advanced colorectal cancer
Authors: Chong G. , Starling N. , Norman A. R. , Brown G. , Thomas J. , Ross P. J. , Cunningham D. C. 
Published: March 2020

13558 Background: There is preclinical evidence that gemcitabine has activity in colon cancer. However, previous clinical studies have not clearly demonstrated activity of gemcitabine given as a 30 minute infusion. Prolonged exposure of colon cancer cell lines to gemcitabine appears to have greater antitumour effect compared to shorter exposure (Kornmann et al, Eur J Surg Oncol 2000). Methods: Patients with progressive, pretreated metastatic colorectal cancer received gemcitabine 1500 mg/m2 at a fixed dose rate of 10 mg/m2/min (150 minutes) D1, 8, 15 every 28 days. The primary endpoint was disease control rate (CR/PR/SD) assessed by CT scan. Using a 2-stage statistical design, a total of 37 patients were required to demonstrate at least a 25% disease control rate with 90% power and a 1-sided alpha of 0.05. The 1st accrual stage required at least 6/17 pts to obtain disease control, prior to proceeding to the 2nd stage. Results: 16 patients with a median age of 63 years were treated. The median number of prior lines of chemotherapy was 3 (range: 1–5). The median number of administered gemcitabine doses was 5.5 (range: 1–14). 3 patients achieved SD after 3 cycles, but subsequently progressed. 13 patients either progressed prior to the first scheduled CT scan or had declining performance status requiring removal from the study. 1 patient experienced transient reduction in serum CEA of > 50%. Median progression-free survival was 77 days (95% CI 61–93). Grade 3/4 neutropenia occurred in 4/1 pts; grade 3/4 thrombocytopenia in 6/0 pts. 2 pts had grade 3 infection. As only 3/16 pts achieved disease control, it was not possible to proceed to the 2nd stage and the study was closed to accrual. Conclusions: Gemcitabine administered by fixed dose rate infusion has minimal activity in heavily pretreated patients with advanced colorectal cancer. Gemcitabine monotherapy is not recommended in this patient population. No significant financial relationships to disclose.
Nutritional status of colorectal cancer patients and its changes during primary treatment
Authors: Meyer L. , Gastinger I. 
Published: March 2020

13577 Background: The nutritional status of oncological patients has become a subject of growing scientific interest because of its prognostic significance and the resulting therapeutic possibilities. Apart from the documentation of the nutritional status at the time of diagnosis the influence of the intensive primary treatment plays a major role. Methods: From October 2002 to December 2004 data on the nutritional status of 106 colorectal cancer patients were documented prospectively. The primary assessment of the nutritional status was performed with the SGA (Subjective Global Assessment). Additionally, a Body Impedance Analysis (BIA) was carried out and repeated at the day of surgery and the fivth and tenth postoperative day. Results: In the three groups according to the SGA (A: well nourished, B: moderately malnourished, C: severely malnourished) we found 27 patients to be group A, 76 patients group B and only 3 patients group C. The data of the BIA showed phase angle of 5.7°, 5.0° and 3.7°, the index of Extracellular Mass and Body Cell Mass (ECM/BCM) the figures 0.8, 1.0 and 1.6. The data remained in the same range up to the day of surgery and got worse in the early postoperative period (until 5. postoperative day). In the late postoperative (day 6 to 10) we could notice a stabilisation, the preoperative values were not achieved until demission. Conclusions: Patients with colorectal cancer are moderately malnourished in about 75%, but severely malnourished in only very few cases. The period of preoperative diagnostics does not lead to an impairment of the nutritional status. After surgery and in the early postoperative period the nutritional status is considerably affected and does not reach the primary level until demission. In this field the multimodal perioperative concepts seem to be a chance to diminish the nutritive deficit and to discharge the patient in a better condition after primary treatment. No significant financial relationships to disclose.
A phase I study of S-1 plus weekly docetaxel in patients with metastatic gastric cancer
Authors: Park S. R. , Yu M. S. , Kim C. G. , Choi I. J. , Lee J. S. , Kim Y. W. , Ryu K. W. , Lee J. H. , Bae J. M. , Kim H. K. 
Published: March 2020

14005 Background: We conducted a study to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S-1 plus weekly docetaxel in pts with metastatic gastric cancer (MGC), and to recommend a dose for phase II study Methods: Pts with MGC, age ≥ 18 yrs, ECOG PS 0–2, adequate organ function, and no or 1–2 prior chemotherapy were eligible. S-1 was given twice daily, p.o. on D1–14 and docetaxel i.v. on D1, 8, q 3 wks. Each cohort of 3 pts was treated with escalating doses of S-1/docetaxel at 60/25 (level I), 70/25 (level II), 70/30 (level III), 80/30 (level IV), 80/35 (level V), 90/35 (level VI), and 90/40 mg/m2 (level VII). The DLT pertaining to 1st cycle only was obtained. Results: Thirty pts with median age of 50 yrs (range: 27–71) with MGC received a median of 8 cycles (range: 1–12). A total of 222 cycles were administered. DLTs were; G3 elevated liver enzyme at level I (1/6 pts), gastric perforation at level V (1/6), G3 diarrhea and febrile neutropenia (FN) with G3 nausea/anorexia/fatigue at level VI (2/6), and FN and neutropenic infection (NI) with G3 stomatitis at level VII (2/3). After DLT occurred in 2 of 3 pts in level VII, 2 of additional 3 pts enrolled at level VI had DLT. Then, 1 pt developed DLT among additional 3 pts enrolled at level V. Therefore, MTD and recommended dose (RD) were level VI and V, respectively. There were 2 CRs, 17 PRs with response rate of 65.5% (95% CI 48.2–82.8%), 8 SDs and 2 PDs among 29 efficacy-evaluable pts. Conclusions: MTD for this regimen was S-1 90 mg/m2/d + docetaxel 35 mg/m2 and RD was S-1 80 mg/m2/d (D1–14) + docetaxel 35 mg/m2 (D1, 8). (Supported by National Cancer Center Grant; Docetaxel and S-1 were provided by Sanofi-Aventis Korea and Jeil Pharm. Co., respectively) [Table: see text] No significant financial relationships to disclose.
Phase II study of gemcitabine and cisplatin in previously untreated metastatic or recurrent advanced esophageal cancer: A Chinese esophageal cancer group
Authors: Huang J. , Fan X. Q. , Chen L. , Liu N. A. , Cai G. R. , Zhang R. X. , Wang W. J. , Sun Y. 
Published: March 2020

14015 Background: Esophageal cancer is one of the most frequent malignancies and the second leading cause of death from cancer in some area in China. The combination of gemcitabine and cisplatin acts synergistically in the treatment of some solid tumors, such as lung cancer, head and neck cancer etc. We performed a phase II trial of gemcitabine in combination with cisplatin for esophageal cancer. The antitumor response, toxicity and survival of patients treated with the two-drug regimen were evaluated. Methods: Patients with chemotherapy-naive metastatic or recurrent advanced squamous cell carcinoma of the esophagus were treated with Gemcitabine at 1000mg/m2 over 30–60 minutes on days 1, 8 and cisplatin 40mg/m2 on days 1, 2. Cycles were repeated every 21 days. Granulocyte colony-stimulating factor (G-CSF) was not routinely administered unless the patient had neutropenia. Results: Thirty-four eligible patients were accrued and 26 patients were evaluable for response. Major objective responses were observed in 15 patients (57.7%), including two complete responses (7.7%) and thirteen partial responses(50.0%). All patients with response were confirmed again after four weeks. 28 patients were evaluable for toxicity. Non-haematological toxicity consisted 7.1% (2 patients) grade 3/4 nausea/vomiting. Myelosupression was the most common toxicity. 39.3% patients occurred grade 3/4 myelosuppression. Conclusion: This cisplatin-gemcitabine regimen was manageable and had significant activity in patients with advanced esophageal cancer. No significant financial relationships to disclose.
Phase II study of capecitabine and irinotecan combination chemotherapy in patients with advanced gastric cancer
Authors: Baek J. , Kim J. , Chae Y. , Cho Y. , Sohn S. , Choi Y. , Shin H. , Chung J. , Cho G. , Yu W. 
Published: March 2020

14037 Background: Several studies have shown the efficacy of capecitabine and irinotecan combination chemotherapy for advanced colorectal cancer, while no results have yet been reported for advanced gastric cancer. Accordingly, the current study evaluated the efficacy and safety of a combination regimen of capecitabine plus irinotecan in patients with advanced gastric cancer. Methods: Patients with previously untreated metastatic or recurrent, measurable gastric cancer received oral capecitabine 1000 mg/m2 twice daily from day 1 to 14 and intravenous irinotecan 100 mg/m2 on days 1 and 8, based on a 3-week cycle. Results: Forty-one patients were enrolled in the current study, among whom 38 were assessable for efficacy and 40 assessable for toxicity. Three complete responses and 16 partial responses were confirmed, giving an overall response rate of 46.3%. At a median follow-up of 269 days, the median time to progression and overall survival were 5.1 months and 8.6 months, respectively. Grade 3/4 neutropenia occurred in 4 patients and grade 3 febrile neutropenia was observed in 2 patients. Grade 3 diarrhea and grade 2 hand-foot syndrome occurred in 6 patients and 8 patients, respectively. Conclusions: The combination of capecitabine and irinotecan was found to be well tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important first-line treatment option for advanced gastric cancer. No significant financial relationships to disclose.
Phase II study of sequential non-cross-resistant chemotherapy using weekly 24-hour infusion of cisplatin, high-dose 5-fluorouracil and leucovorin (P-HDFL) followed by weekly docetaxel and irinotecan (DI) for recurrent or metastatic gastric cancer: an interim analysis
Authors: Yeh K. , Hsu C. , Lu Y. , Hsu C. , Kuo S. , Huang C. , Shen Y. , Hsiao C. , Yang C. , Cheng A. 
Published: March 2020

14063 Weekly 24-hour infusion of high-dose 5-FU and leucovorin (HDFL)-based regimens are highly effective for advanced gastric cancer (AGC). Although the response rate has been improved, the overall survival (OS) was not significantly prolonged. To prolong the OS, we designed a sequential chemotherapy strategy incorporating non-cross-resistant docetaxel and irinotecan (DI). All patients had patho/cytologically confirmed recurrent/metastatic chemonaive AGC, at least 1 measurable lesion, a fasting serum triglyceride level > 70 mg/dl, adequate hepatic, renal, and marrow functions. Induction regimen was P-HDFL (cisplatin 35 mg/m2, i.v. 24-hr, D1, 8; 5-FU 2600 mg/m2 and leucovorin 300 mg/m2, i.v. 24-hr, D1, 8, 15; every 4 wks), and consolidation regimen was weekly DI (docetaxel 30–35 mg/m2/wk, i.v. 30-min, then irinotecan 60–70 mg/m2/wk, i.v. 30-min, D1, 8, 15; every 4 wks). Patients with inferior conditions (prior Gr4 neutropenia or Gr3/4 infection, poor marrow reserve with delayed hemogram recovery, poor nutritional status or ileus) started with dose-modified DI (D: 30, I: 60 mg/m2/wk). For CR patients by P-HDFL, 3 cycles of DI were given; and for PR or SD patients, DI was continued till 2 cycles after CR, disease progression, or unacceptable toxicities. Between Jun. 2000 and Dec. 2005, 23 patients were enrolled (M:11, F:12) with a median age of 52 (37–68). Total 114 cycles (median: 6, range: 2–8) of P-HDFL were given. Overall RR was 60.9% (38–80%, 95% C.I.) with 3 CRs and 11 PRs. Gr3/4 toxicities: neutropenia (14%), infection (4.4%), thrombocytopenia (1.6%), diarrhea (5%), and vomiting (7%). Gr1/2 hand-foot syndrome was noted in 11% of cycles. Patients with CR, PR, and SD were treated with weekly DI regimen. Total 59 cycles (median: 4, range: 1–10) of weekly DI were given. Gr3/4 toxicities: neutropenia (30.5%), infection (13%), thrombocytopenia (2%), and diarrhea (17%). Median OS of the whole intent-to-treat group is 18 months (3 to 62+), and median OS of 14 responders of P-HDFL is 20 months (7 to 62+). This sequential non-cross-resistant strategy is very effective for prolongation of OS in advanced AGC. No significant financial relationships to disclose.