bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic significance of fascin overexpression in rectal cancer
Authors: Roh M. S. , Lee J. H. , Kwon H. , Park K. J. , Choi H. J. , Cho S.
Published: March 2020

13517

Background: Fascin is an actin-bundling protein that induces cell membrane protrusions and increases motility of normal and various transformed epithelial cells. In normal epithelial cells, fascin expression is usually absent or very low, but is often upregulated in several types of human neoplasms. However, the clinicopathological features of fascin expression in rectal cancer are still unknown. Methods: Immunohistochemistry for fascin was performed in 79 rectal cancers. Staining more than 5% of tumor cells was recorded as positive immunoreactivity. Results: Overall, fascin immunoreactivity was detected in 63 (79.7%) out of a total 79 cases. Increased immunoreactivity of fascin was sometimes seen at the invading edge of the tumor. Fascin expression was correlated with TNM staging (p=0.001), positive lymph node metastasis (p=0.001), tumor budding (p=0.001), lymphovascular invasion (p=0.001) and perineural invasion (p=0.039); however, recurrence was not statistically significant (p=0.068). Overall survival rate of patients with fascin-positive tumors was significantly lower than that of patients with fascin-negative tumors (p=0.012). Conclusions: Therefore, we suggest that the overexpression of fascin in rectal cancer may be implicated not only in tumor growth but also in the development of metastases. Our findings indicate that the immunohistochemical detection of fascin could provide useful information as one of the prognostic factor in rectal cancer.

No significant financial relationships to disclose.
Hepatic metastasectomy following FOLFOX therapy in patients with colorectal metastases
Authors: Arciero C. A. , Salem R. R. , Lacy J. , Sigurdson E. R. , Hoffman J. P. , Watson J. C. , Joseph N. , Cooper H. S. , Meropol N. J. , Burtness B.
Published: March 2020

13523

Background: Advances in systemic therapy for metastatic colon cancer may render patients (pts) candidates for hepatic metastasectomy (HM) with curative intent. We retrospectively reviewed our experience with HM following oxaliplatin chemotherapy. Methods: Pts were identified from the records of 5 surgeons who performed HM at two institutions. Pts were included if FOLFOX (bolus 5-FU/leucovorin d1 or d 1 + 2, followed by 46 hour 5-FU infusion; oxaliplatin 85–130mg/m2 d 1 q 14 d) chemotherapy had been given for > 1 cycle prior to HM and complete resection of hepatic metastases was achieved. Data on radiographic (RECIST) and pathologic response and outcome were collected. Pathologic complete response (pCR) was defined as no residual cancer. Near pCR was defined as residual mucin in the liver, without residual cancer cells, or necrosis with atypical glands. Results: Thirty-six pts were identified. Males 21/36, median age 55 (range 37–77), rectum/rectosigmoid primary 5 (13.9%), adenocarcinoma 100%, synchronous metastases or metastases within 6 months (m) of primary diagnosis 24/32 (75%), median cycles of FOLFOX = 7 (range 2 to >30), bevacizumab (B) 9 (25%). Mean number of hepatic lesions pre-chemotherapy 1.9 (range 1–7), tumor size 1 to >10cm. Radiographic responses to pre-operative FOLFOX included partial response (PR) 9/30 (30%), CR 2/30 (6.7%), progressive disease 3/30 (10%), stable disease 16/30 (53.5%). Operations included right (R) hepatectomy 12, extended (ext) R hepatectomy 3, partial R hepatectomy 2, left (L) hepatectomy 3, partial L hepatectomy 1, ext L hepatectomy 1, trisegmentectomy 2, caudate lobectomy 1, multiple wedge resections ± radiofrequency ablation 7. pCR 2 (5.6%); near pCR 3 (8.3%). At a median follow up of 12.9 m from HM, 9/36 (25%) recurred; liver only (3), portal lymph nodes (1), other extrahepatic sites (5). One pt died at 18.3 m. Conclusions: HM after FOLFOX chemotherapy, with or without B, results in a high progression-free and overall survival at 12.9 m. This retrospectively identified population included pts with conventionally adverse prognostic features including rectal cancers, synchronous metastases, large lesions and/or high lesion number. Prospective studies of the utility of pre-HM chemotherapy are warranted.

[Table: see text]
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.
Preliminary results of a phase II trial of FOLFOX4 regimen in Chinese patients with unresectable primary liver cancer
Authors: Qin S. K. , Wang Y. J. , Wu Q. , Xing B. C.
Published: March 2020

14065

Background: Primary liver cancer (PLC) is the 3rd most common cancer in whole China. Development of systemic chemotherapy for the patients not eligible for operation as well as TACE commonly have been required. Oxalipaltin (Eloxatin)+ 5-FU/LV, namely FOLFOX 4 regimen was tried to investigate its efficacy and safety in inoperable PLC. Methods: It was an open-label, single arm and multi-center phase II study to explore RR, DCR,TTP and MST. All the pts had pathologically confirmed inoperable PLC with/without distant metastasis. The pts were treated with the standard FOLFOX 4 regimen, that is OXA 85mg/m2 d1; LV 200mg/m2 IV 2hrs d1,2; 5-FU 400mg/m2 bolus, d1,2 and 5-FU 600mg/m2 CIV 22hrs d1,2; q2w upto 6 cycles or until progression. Tumor evaluation was done every 6 weeks using RECIST criteria. Neurotoxicity was evaluated by Eloxatin specific neurotoxicity criteria (Sanofi-Aventis Co.Ltd) and other toxicities by the NCI CTC AE version 2.0. Results: From July 2004 to Sep. 2005, 27 pts (21 male, 6 female) were recruited from the 4 cancer centers with average age of 56 ±13 years old. 25 patients (92.6%) had hepatocellular carcinoma, and 2 (7.4%) cholangiocellular carcinoma. 15 pts (55.6%) had metastatic disease. 1 pt received liver transplantation before inclusion. The median number of cycles was 4 per pt. 26 pts were evaluable for efficacy and safety. The RR was 19.2% (5/26; 1 CR and 4 PR), and DCR 57.7% (15/26; including 10 SD). 4 of the 5 responsive pts had hepatocellular carcinoma, and 1 had cholangiocarcinoma. Serum AFP level was significantly decreased (mean 131,890.4ug/dl at the baseline and 1,298.6ug/dl after 6 cycles) for the first 16 pts. The first 16 pts’ safety data were available in detail: 11 NCI grade 3/4 events were observed from a total of 76 cycles administered: including 5 neutropenia, 3 leucopenia, 1 thrombocytopenia, 1 infection and 1 liver dysfunction. Grade II & III neurotoxicity was found in 3 & 2 patients respectively. The TTP,MST and further safety data were under follow-up. Conclusions: The preliminary data of the FOLFOX 4 regimen for the advanced Chinese pts with inoperable PLC have shown encouraging results with the better efficacy and favorable safety profile. Further exploration in this area is warranted, especially in hepatocellular carcinoma.

No significant financial relationships to disclose.
Retrospective review of patients with adenocarcinoma of the pancreas and ovarian metastasis: Clinical characteristics, treatment strategies, and survival data
Authors: Falchook G. S. , Varadhachary G. R. , Wolff R. A.
Published: March 2020

14068

Background: Ovarian metastasis from pancreatic adenocarcinoma is rare, and data on clinical features, treatment, and survival are limited. Methods: Charts of 19 patients with pancreatic adenocarcinoma and ovarian metastasis identified by the UTMDACC tumor registry from 1984–2005 were reviewed. Results: Clinical characteristics and survival data are in the Table. Data were limited in patients seen for single-visit second-opinion consultation or for whom only pathology was available. Other synchronous metastatic sites included peritoneum (11), liver (9), lung (5), fallopian tubes (4), uterus (2), colon (2), appendix (1), and brain (1). Ovarian metastasis size varied from “studding” to 20 cm. Among the 12 patients known to have received chemotherapy, 10 underwent resection of the ovarian metastasis. Among these, 5 patients achieved a partial response (PR) in liver metastases, peritoneal metastases, or the pancreatic primary. 3 patients received chemotherapy before resection of the ovarian metastasis, but none demonstrated a response in the ovarian metastasis. Chemotherapy regimens achieving a PR included cisplatin/paclitaxel, gemcitabine/oxaliplatin, gemcitabine/cisplatin, gemcitabine/C225, and gemcitabine/docetaxel/capecitabine. Conclusions: Pancreatic adenocarcinoma with ovarian metastasis is rare, and patients often present with an ovarian mass prior to the pancreatic adenocarcinoma diagnosis. Surgical resection of ovarian metastasis may play a palliative role in symptomatic patients since the survival of these patients appears favorable and response of ovarian metastasis to chemotherapy has not been observed. [Table: see text]

No significant financial relationships to disclose.
Gemcitabine + cisplatin (GEM+CIS) in combination with regional hyperthermia (RHT) in second-line therapy of gemcitabine-refractory metastatic pancreatic cancer
Authors: Tschoep K. E. , Milani V. , Schmidt G. , Schiel X. , Abdel-Rahman S. , Kuhlencordt M. F. , Salat C. , Maier V. , Heinemann V. , Issels R. D.
Published: March 2020

14073

Background: Our completed phase III trial comparing GEM + CIS vs. GEM alone showed good efficacy for the combination arm in 1st-line therapy (ASCO abstr. No. 1003, 2003). Based on the rationale of chemosensitization of CIS by RHT we are performing a prospective phase II study with GEM + CIS combined with RHT. Methods: Until 8/2005 12 pts with metastatic pancreatic adenocarcinoma who failed GEM-based 1st-line-therapy were enrolled in this study. One cycle consisted of GEM (1000mg/m2) on d1 followed by CIS (25mg/m2) on d2 and d4 combined with RHT (BSD system). A total of 2 blocks each of 4 cycles were given biweekly. The main endpoints were time to second progression (TTP2) and 1-year event free survival (1-yr-EFS). TTP2 and EFS were defined as time from start of 2nd-line therapy until progression of disease or death. Response (RECIST) was evaluated after 4 and 8 cycles of therapy. Results: Pt characteristics: median age 60; M:F=8:4. Median time to first progression (TTP1) was 6 months (95% CI:2–7). 8/12 pts received all 8 cycles. No toxic death and no grade 4 toxicity occurred. In 12/2005 10/12 pts were evaluable for this study. Control of disease (1CR, 2MR, 4NC) and progression (3PD) occurred in 70% and 30% respectively. The median TTP2 is 8 months (95% CI: 2–13) and the 1-yr-EFS is 32% (95% CI:3–61). 7 pts are alive at 12/2005. Conclusions: Our ongoing study (EudraCT-No 2005–003855–11) using RHT combined with GEM + CIS shows promising antitumor activity with a very encouraging TTP2 and median 1-yr-EFS in the 2nd-line treatment of GEM-refractory metastatic pancreatic cancer.

[Table: see text]
Preliminary results for the combination of docetaxel, oxaliplatin and capecitabine as a first-line treatment for metastatic oesophagogastric cancer
Authors: Viteri S. , Rodríguez J. , González Cao M. , De La Cámara J. , Chopitea A. , Viudez A. , Reyna C. , Olier C. , García-Foncillas J.
Published: March 2020

14076

Background: Chemotherapy remains the main treatment option for metastatic oesopagogastric cancer (MOC) patients (Pts). First-line regimens have proved a slight but significant increase in quality of life and survival, but a standard regimen has not been defined yet. Several new drugs, as Docetaxel (D), Oxaliplatin (O) and Capecitabine (C) have demostrated activity in MOC. They have shown synergy in preclinical models and activity in previous phase II trials. The purpose of our study is to asses activity and feasibility of the combination of D, O and C as first-line chemotherapy in MOC patients. Methods: MOC patients, with good ECOG performance status and chemonaive are eligible. Pts receive D 60 mg/m2 day 1, O 85 mg/m2 day 1 and oral C 650mg/m2 bid d1–14 every 3 weeks. Primary endpoints are response according to WHO criteria and toxiciy assesment according to NCI.CTCAE v3.0. Results: From November 2004 to December 2005, 17 Pts have been enrolled. Median ECOG PS is 1 (0–2) M/F:9/8. Median age is 57 years (38–68) Primary tumor are gastric carcinomas (82%) and lower oesofagus carcinomas (18%). Metastatic sites included peritoneum 58%, liver 23% and lung 23%. Median number of cycles is 5 (1–7) Treatment is well tolerated with no toxic deaths. NCI grade 3–4 toxicities include 2 Pts (11.8%) with grade 4 neutropenia and one of them developed septic shock; 2 Pts with grade 3 asthenia, 1 Pt with grade 3 vomiting and 1 patient with grade 3 neurotoxicity. Main NCI grade 2 toxicities are dhiarrea (35.3%) and neurotoxicity (23.5%). 13 Pts have been evaluated for response until now: 9 Pts have a confirmed Partial Response (69.2%) and 2 of them underwent salvage surgery; 3 Pts have Stabilized Disease and 1 Pt Progression Disease. Median time to progression and median overall survival have not been reached yet and the study is still ongoing. Conclusions: The combination of D, O and C at the dosses and schedule used in this trial is effective in MOC with a manageable toxicity profile

No significant financial relationships to disclose.
Postoperative chemoradiation for resected gastric cancer—The tolerability of the Macdonald regimen in the routine clinical practice setting in Israel
Authors: Kundel Y. , Idelevich E. , Purim O. , Kovel S. , Pfeffer R. M. , Catane R. , Karminsky N. , Stemmer S. M. , Fenig E. , Sulkes A. , Brenner B.
Published: March 2020

14077

Background: Postoperative chemoradiation as per the Intergroup 116 trial (“the MacDonald regimen”) is considered standard for completely resected high risk gastric cancer. However, concerns remain with regards to the toxicity of this regimen. To evaluate the safety and tolerability of this regimen in a routine clinical practice setting, we analyzed retrospective date of several Oncology Institutes in Israel. As we did not expect a different toxic profile in patients (pts) with positive margins (R1 resection), these were studied together with pts that underwent complete resection (R0). Methods: Treatment was administered according to the original Macdonald report. Overall and disease free survival rates were calculated using the Kaplan-Meier method. Results: Between 6/2000 and 9/2005 100 pts who had R0 (81%) or R1 (19%) resection of locally advanced gastric adenocarcinoma received post-operative chemoradiation; 62% were male and the median age was 64 years (range, 25–78); 77% had T≥3 tumors and 85% had N+ disease; 91% of the pts completed radiotherapy and 62% completed the entire chemoradiation plan. Reason for discontinuation was toxicity in all cases; 48% of the pts had grade ≥ 3 toxicity (30% grade 3 and 23% grade 4), 32% were hospitalized at least once for supportive care .Three patients (3%) died of toxicity: grade 4 diarrhea (1), neutropenic sepsis (1), and neutropenic sepsis complicated by small bowel gangrene (1).The most common hematological toxicity was neutropenia, which was grade ≥3 in 30% of the pts and was complicated by infection in 17%. The most common non-hematological toxicities were nausea, diarrhea and fatigue. With a median follow-up of 24 months (range, 3–64 months), 68% of the R0 patients remain alive and 64% are free of disease. Median disease free survival is 54 months and median overall survival has not been reached. Conclusions: In our experience, postoperative chemoradiation as per Intergroup 116 seems to be highly toxic, with a mortality rate higher than reported in that trial. Preliminary efficacy data seems comparable to the original report.

No significant financial relationships to disclose.
Is hyperglycemia a prognostic factor in pancreatic cancer?
Authors: Mekan S. F. , Safa M. M. , Komrokji R. S. , Nahleh Z. A. , Jazieh A. R.
Published: March 2020

14078

Background: Pancreatic hyperglycemia is one of the manifestations of pancreatic cancer.The purpose of this study is to explore the prevalence and significance of hyperglycemia at the time of diagnosis of pancreatic cancer. Methods: We reviewed retrospectively cases presenting to our institution with diagnosis of pancreatic carcinoma between 1999–2003. Hyperglycemia was defined as a blood sugar of greater than 140mg/dL. Results: There were 155 cases diagnosed with pancreatic cancer. Out of these, 67 (43.2%) were males and 71(45.8%) were females. The mean age was 63 years. Staging was reported in 134 patients: 19 patients (14%) were stage I, 23 (17%) stage II, 40 (30%) stage III and 52 (39%) stage IV. Median survival time was 8 months. Thirty-four (22%) patients had prior history of diabetes mellitus and were excluded from subsequent analysis. Sixty-four patients out of 121 patients (53%) were found to be hyperglycemic. These patients had no prior history of diabetes mellitus or were diagnosed with diabetes within six months. There was no difference between hyperglycemic patients and normoglycemic patients regarding age, sex, race, tumor location, smoking history, history of pancreatitis and hypertension. Hyperglycemic patients were more likely to have history of alcohol use compared to normoglycemic patients (p value = 0.005, OR = 4.07). Hyperglycemic patients were less likely to present with stage IV disease as compared to normoglycemic patients (25% vs. 55%) (p-value 0.002). The median survival in hyperglycemic patients was significantly longer than in normoglycemic patients (12 vs. 6 months, p-value = 0.02).There was a trend towards better survival among stage IV hyperglycemic patients as compared to normoglycemic patients (13 months vs 3 months) (p-value 0.38). Conclusions: In this retrospective analysis, 53% of pancreatic cancer patients without diabetes had hyperglycemia at presentation. These patients presented at an earlier stage compared to normoglycemic patients and had significantly longer survival. The impact of hyperglycemia on survival could be related to earlier presentation or difference in the tumor biology. The clinical significance of hyperglycemia in pancreatic cancer should be further studied in prospective fashion.

No significant financial relationships to disclose.
Phase II study of irofulven in recurrent or metastatic gastric cancer: A Cancer Therapeutic Research Group (CTRG) study
Authors: Chung H. C. , Yeo W. , Rha S. Y. , Boyer M. , Ong S. Y. , Lim R. , Zee B. , Roh J. K. , Goh B. C. , Chan A. T.
Published: March 2020

14105

Background: Cytotoxic chemotherapy has been widely used in patients (pts) with advanced or metastatic gastric cancer, but the reported high response rates in phase II settings have not been confirmed by randomized trials. Moreover, the therapeutic impact on survival has been modest. The purpose of this study was to evaluate Irofulven, a DNA interacting acylfulvene analog, as first line therapy for pts with recurrent or metastatic gastric cancer. Methods: The main eligibility criteria were: Histologically or cytologically confirmed disease; age > 18 yrs; ECOG ≤ 2; measurable disease; no prior chemotherapy for recurrent or metastatic disease; life expectancy > 3 months. Irofulven was given at 0.45 mg/kg i.v. over 30-min infusion (max. 50 mg), on Day 1 and 8, every 3 weeks. The primary endpoint was treatment response and toxicity; the secondary end-point was survival. A 2-stage phase II design was used. In the first stage, the target enrollment was 20, if ≤ 2 responses were observed, the study would be stopped and the treatment concluded to be ineffective; if ≥ 6 responses were observed, the study drug would be concluded to be active. Otherwise, another 15 pts would be entered into the second stage. Survival was constructed using the Kaplan-Meier method. All patients entering the trial were included in the survival analysis. Results: 23 pts were entered into the first stage. The median no. of cycles per pt was 2 (range: 1–6). 2 pts (9%) had ≥ 1 week delay in administration of subsequent cycle of chemotherapy. For the day 8 chemotherapy, 7 pts (30%) required dose reductions; 5 (22%) had dose omitted. 22% and 17% pts developed grade 3/4 anemia and neutropenia respectively. There was no grade 4 thrombocytopenia or neutropenic fever. Of the 20 evaluable pts, no responses was observed, 3 pts had stable disease after 2 cycles of treatment which was not confirmed by a further assessment. Median overall survival was 6.05 months (95% CI 4.55–9.39). Conclusions: Irofulven was tolerated at the described dose but showed no evidence of antitumor activity in patients with advanced gastric cancer. Acknowledgement: The study was sponsored by the Division of Cancer Treatment and Diagnosis, National Cancer Institute, U.S.A, and its collaborator MGI Pharma, Inc.

No significant financial relationships to disclose.
mTOR inhibition affects primary liver cancer
Authors: Rizell M. , Cahlin C. , Olausson M. , Hafstrom L. , Andersson M. , Lindner P.
Published: March 2020

14106

Background: Due to extent of tumour and underlying liver disease primary liver cancer, hepatocellular(HCC) as well as cholangiocellular(CCC), has extremely poor prognosis. The tyrosinekinase and mTOR inhibitor sirolimus, is registered for preventing allograft rejection. It retard experimental liver tumours in rats, and has antiangiogenic effects as well. Methods: Patients with a nonoperable HCC or CCC, with a Karnofsky >70, and the diagnosis confirmed by biopsy or alfa-fetoprotein (>700ug/ml) were eligible. Ethic committee approved the study and informed consent was signed. The daily Sirolimus dose was adjusted to a 6–10 μg/L through-concentration.Twenty patients were to be enrolled in a nonrandomized study. The primary endpoint was to detect a radiological tumor response rate, defined by RECIST criteria, and secondary endpoint was to study the safety profile. CT or MRI were repeated every third month. The study was approved by the Etic Committee of Göteborg University. Results: Eleven patients with HCC and nine with CCC were included. Overall respone rate was 5%, which ocurred in a patient patient with HCC. The PR lasted for 15 months (RR 9% for HCC). Four patients with HCC had SD for median 7 months (range 5–18). Of the patients with CCC four had SD. Median duration of SD was 4 months (range 1 - 7). Median survival for patients with HCC was 7 months (range 2–20) and CCC 4 months (range 2–24) Discussion: There is low evidence supporting the use of chemotherapy for primary liver cancer. For HCC, one PR and 4 SD in this pilot study indicate that sirolimus might be of interest to study in a phase II trial, since the toxicity of sirolimus was low. In the european SILVER study,the impact of sirolimus for patients transplanted for HCC will be clarified. Experimentally, the antiangiogenetic effects of sirolimus has been boosted by combining with 5-FU and gemcitabine. This might translate to impoved response rate also for liver cancer. Conclusions: This pilot study suggests that sirolimus have a tumour effect in patients with HCC.

No significant financial relationships to disclose.
Chemotherapy with FOLFOX IV in advanced gastric cancer
Authors: Garrido. M. A. , Melgoza G. , Galindo H. , Madrid J. , Sanchez C. , Alvarez M. G. , Orellana E.
Published: March 2020

14112

Background: Gastric cancer is the first cause of mortality for cancer in Chile. 65% is observed in advanced form and the median survival without surgery is 5,4 months. We hypothesised that chemotherapy and specially FOLFOX IV is an active regimen and has low toxicity in patient with advanced gastric cancer. The main evaluated objectives were: response, toxicity and survival of patient with advanced gastric cancer. Methods: Patients with gastric adenocarcinoma, stage IV that accepted chemotherapy with FOLFOX IV in any time of evolution were included. The evaluation of response was obtained with CT scan every two month. The characteristics of patients, chemotherapy responses, toxicity and global survival were analysed. Results: Between November 2003 and October 2005, 20 patients were included, the median age was 51,5 years (range 28–67), 80% male. Hepatic, peritoneal and lung metastases were the principal places of dissemination. The response rate in first line was: PR 66%, SD 17%, with overall response of 83% (12 patients). In second line the response was: PR 37%, SD 63% (8 patients). The average of treatment was 5,5 months. The median of response was 5 months (2–12). The median overall survival was 12 months. 50% of patients showed toxicity; digestive grade 2 in 2 patients, neurological grade 2 in 4 patients and only 1 patient showed grade 3 toxicity. Conclusions: FOLFOX IV is an active chemotherapy regiment with low toxicity profile in advanced gastric cancer. With these results we propose a Phase III trial would be feasible to perform.

No significant financial relationships to disclose.
Combination of irinotecan, oxaliplatin and cetuximab for patients with metastatic pancreatic cancer
Authors: Roach M. , Lee F. , Rabinowitz I. , Parasher G. , Heywood G.
Published: March 2020

14135

Background: Gemcitabine-based chemotherapy is considered standard approach for patients with metastatic pancreatic cancer but the results remain unsatisfactory with survival averaging about 6 to 10 months. Cell line study indicates more than 90% of pancreatic cancer cells express EGFR receptor. We therefore explore the use of non-gemcitabine-containing regimen and add an EGFR inhibitor. Method: We initiated a regimen with irinotecan 120 mg/m2, oxaliplatin 85 mg/m2, and cetuximab 400 mg/m2 first dose followed by 250 mg/m2 for all subsequent doses delivered every 14 days for patients with metastatic pancreatic cancer. Results: From 1/2005 to 12/2005, a total of 5 patients were treated. Two males and three females, age 59 to 78. Three presented with metastatic disease. One had Whipple’s procedure then had disease recur 2 months post-surgery. One had locally advanced disease and progressed 10 months after concurrent chemoradiation. Grade III/IV neutropenia, anemia developed in 1/5 patients. Grade III/IV diarrhea and nausea/vomiting developed in 3/5 patients. Grade III/IV fatigue, anorexia developed in 4/5 patients. The non-hematologic toxicity was the main reason for dose reduction. 4 had CT scan for response evaluation. The fifth patient completed first cycle of treatment on 1/3/2006 and had CA19–9 dropped from 15,900 to 9,398 u/ml (40% decline). By CT scan, partial response rate is 75% as shown in the table. So far, two patients have died, 5 and 10 months since initiating treatment, one from recurrent hepatic abscess and one from fungus infection. Conclusions: This combination delivered every other week appears promising for patients with metastatic pancreatic cancer. The planned phase II trial will adopt a lower dose approach with irinotecan 90 mg/m2, oxaliplatin 60 mg/m2, and cetuximab 250 mg/m2. [Table: see text]

No significant financial relationships to disclose.