Recurrent Gastrointestinal Cancer Research Articles

Real-world data of anamorelin in advanced gastrointestinal cancer patients with cancer cachexia

BackgroundCancer cachexia is characterized by the loss of body weight (BW) and anorexia. Anamorelin (ANAM) is a selective ghrelin receptor agonist with appetite-enhancing anabolic action. The ONO-7643-05 trial demonstrated that ANAM increased lean body mass and improved anorexia in a Japanese population. However, the clinical outcomes of patients on ANAM have not yet been reported.Patients and methodsWe investigated the clinical outcomes of patients with unresectable, advanced, or recurrent gastrointestinal cancer (colorectal, gastric, or pancreatic cancer) who were treated with ANAM between April 2017 and August 2022. Cachexia was defined as the presence of anorexia and a loss of ≥ 5% of BW within 6 months. To evaluate the response to ANAM, the patients who had discontinued ANAM within 3 weeks were excluded. Response to ANAM was defined as maintenance of or increase in BW and improved appetite from baseline at every 3-week evaluation. We also collected data on the reasons for the discontinuation of ANAM and the correlation between clinical factors and ANAM response. Safety analysis of ANAM was performed for all patients who received ANAM.ResultsSeventy-four patients were included in this study (49 males and 25 females), with a median age of 67.1 years (range, 36–83). The primary tumors were colorectal cancer in 27 (36.5%), gastric cancer in 20 (27.0%), and pancreatic cancer in 27 (36.5%). The Eastern Cooperative Oncology Group performance status was 0 in 10 (13.5%), 1 in 44 (59.5%), and ≥ 2 in 20 (27.0%). The number of previous chemotherapy regimens was 0 in 20 (27.0%), 1 in 22 (29.7%), and ≥ 2 in 32 (43.2%). ANAM was discontinued within 3 weeks in 28 patients for the following reasons: low-grade (grade 1 or 2) adverse events in 15 patients, ileus in three, grade 3 fatigue in one, progressive disease in one, censored follow-up in six, and unknown reasons in three. The proportion of ANAM responders was 63.6% (95% confidence interval, 47.8–77.6%). Among baseline characteristics, age ≥ 75 attenuated the ANAM response (p = 0.03). ANAM responders showed better disease control with chemotherapy than non-responders (75.0% vs. 37.5%, p = 0.02).ConclusionsANAM may improve the outcomes of patients with gastrointestinal cancer cachexia in clinical practice.

Immune-related adverse events and prognosis in patients with upper gastrointestinal cancer treated with nivolumab

Immune checkpoint inhibitors (ICIs) are increasingly being used for the treatment of upper gastrointestinal cancers [esophageal cancer and gastric cancer (GC)]. They cause imbalances in immunological tolerance, resulting in immune-related adverse events (irAEs). Although irAEs have been reported to be associated with the efficacy of ICIs in some cancers, the relationship between irAEs and prognosis of upper gastrointestinal cancers remains unknown. This study aimed to investigate the prognostic impact of irAEs in patients with advanced or recurrent upper gastrointestinal cancer treated with nivolumab. We retrospectively divided the patients (n=96) who received nivolumab into two groups: the irAEs group (n=41) and non-irAEs group (n=55), according to the Common Terminology Criteria for Adverse Events ver. 5.0. irAEs were significantly associated with good performance status and high serum albumin levels (all P<0.05). The irAEs group had a significantly longer overall survival (OS) than the non-irAEs group [log-rank P=0.003; univariate hazard ratio (HR) =0.36, 95% confidence interval (CI) =0.21-0.65, P<0.01; multivariate HR =0.47, 95% CI =0.26-0.88, P=0.018]. Importantly, in both esophageal cancer and GC, the irAEs group experienced favorable clinical outcomes compared with the non-irAEs group. In the multivariate analysis, male sex (P<0.01), presence of irAEs (P=0.018), and good pretreatment performance status (P<0.01) were independent prognostic factors. Among patients with upper gastrointestinal cancer treated with nivolumab, the prognosis of patients who developed irAEs was better than that of patients who did not develop irAEs. Long-term continuation of nivolumab by early detection of irAEs and an appropriate response to irAEs are important.

Prevalence of elevated Anti-p53 in Chinese patients with upper gastrointestinal or colorectal cancer.

The monitoring of anti-p53 auto-antibodies in the peripheral blood has been used in cancer management; however, their clinical significance alone is limited. This pilot study aimed to describe the prevalence of elevated anti-p53 in newly diagnosed or recurrent upper gastrointestinal cancer or colorectal cancer in Chinese subjects. It also evaluated whether the addition of anti-p53 to a set of established tumor markers would allow for the detection of additional cancer cases than when using these markers alone. A total of 573 subjects, including 187 healthy individuals, 169 patients with upper gastrointestinal cancer and 217 patients with colorectal cancer were included in this observational, prospective study. All subjects were required to provide up to 10 mL of blood. The following biomarkers were measured: anti-p53, carcinoembryonic antigen, cancer antigen (CA)19-9, and CA72-4. At the cutoff of 0.02 µg/mL, the sensitivity of anti-p53 in early-stage upper gastrointestinal cancer and colorectal cancer was 8.16% and 26.4%, and in late-stage disease was 7.81 and 28.0%, respectively. The specificity of anti-p53 in the healthy cohort at this cutoff was 98.4%. By adding anti-p53 to other tumor markers, the sensitivities were increased by 8.88%-9.47% in upper gastrointestinal cancer, and by 18.06%-25.00% in colorectal cancer; specificities decreased by 1%-2%. The addition of anti-p53 to established tumor markers may improve their diagnostic value for patients with colorectal cancer.

Adjuvant Treatment of Recurrent Gastrointestinal Cancer Based on the Concept of Rapid Eehabilitation

Rapid Rehabilitation Surgery (FTS) refers to the method of relieving and reducing the occurrence of surgical stress and complications and accelerating the postoperative rehabilitation of patients through close cooperation between medical care and nursing. Rapid rehabilitation surgery includes preoperative education for patients, reasonable preoperative preparation, good anesthesia and treatment during operation, fine surgical techniques, effective postoperative analgesia, and minimizing various stress reaction factors during perioperative period. Most patients lack understanding of the concept of rapid rehabilitation surgery. The concept of rapid rehabilitation surgery encourages early getting out of bed, early extubation, early recovery of enteral nutrition support, and restriction of fluid replacement. It is different from the public's understanding of postoperative surgery, which may lead to psychological stress in patients. It is of great clinical significance to optimize the nursing measures of the concept of rapid rehabilitation surgery and formulate a nursing plan that accords with the actual situation of patients.

Small intestinal mucosal injury and its risk factors in patients with gastrointestinal cancer who developed complicated fluoropyrimidine-induced diarrhea

BackgroundDiarrhea is a common adverse event of fluoropyrimidine-based chemotherapy. However, limited data are available on the frequency and risk factors of complicated chemotherapy-induced diarrhea (CID) and small intestinal mucosal damage. In this current study, we aimed to determine the incidence of complicated CID and mucosal injury among patients with complicated CID receiving fluoropyrimidine via small bowel capsule endoscopy (CE) and determined baseline risk factors associated with complicated CID.MethodsIn total, 536 patients with advanced or recurrent gastrointestinal cancer who received fluoropyrimidine-based chemotherapy were retrospectively analyzed. Diarrhea was evaluated using the Common Terminology Criteria for Adverse Events version 4. Complicated CID was defined according to the American Society of Clinical Oncology guidelines. To evaluate small intestinal mucosal injury in patients with complicated CID, CE was performed. Multivariate analysis was performed to identify risk factors for complicated CID.ResultsTotal number of 32 (6%) patients developed complicated CID. Complicating symptoms were noted in 25 (78%) patients, with cramping, vomiting, and sepsis being observed in 15 (60%), 8 (32%), and 3 (12%) patients, respectively. Among the 13 patients who underwent CE, 11 (85%) showed abnormal findings. Multivariate analysis revealed that oral fluoropyrimidine administration was a risk factor for complicated CID (odds ratio 2.95; 95% confidence interval 1.06–8.19).ConclusionsDespite the relatively low incidence of complicated CID, mucosal injury of small intestine was common in patients with complicated fluoropyrimidine-induced diarrhea and oral fluoropyrimidine was an independent risk factor.

Dynamic monitoring of serum soluble programmed cell death ligand 1 as a response predictor to chemotherapy in metastatic or recurrent gastrointestinal cancer

BackgroundBiomarkers in serum may have important clinical implications for personalized medicine, including therapeutic guidance, and monitoring of recurrence. The role of programmed cell death ligand 1 (PD-L1) expression as a tumor biomarker remains controversial. In this study, we aimed at determining the changes of soluble PD-L1 (sPD-L1) during first-line chemotherapy and assessing the association with treatment response and progression-free survival (PFS) of patients with advanced gastrointestinal cancer.MethodsBlood samples from 115 gastrointestinal cancer patients who have not received any previous systemic chemotherapy for recurrent or metastatic disease were collected at the time of diagnosis and each response evaluation. Serum of sPD-L1 expression was tested by enzyme-linked immunosorbent assay (ELISA). The associations between the baseline level of serum sPD-L1 and clinical-pathological characteristics and prognosis were analyzed. we further dynamically monitored the level change of serum sPD-L1 during treatment and analyzed its relationship with clinical-pathological characteristics, chemotherapy response and prognosis.ResultsAmong 115 metastatic gastrointestinal patients, the median serum sPD-L1 level was 0.777 (range, <0.156–6.680) ng/mL. In most cases, changes in sPD-L1 level correlated with treatment response. Patients with values of serum sPD-L1 decreasing after chemotherapy had better tumor response and median PFS compared with patients with values increasing after chemotherapy (ORR, 88.3% vs. 54.0% P=0.000005 and PFS, not reached vs. 27 months, P=0.00026). D-values of sPD-L1 in patients with progressive disease (PD) were observed increasing from 0.406 to 1.097 ng/mL between pre- and post-chemotherapy, while in those with better tumor response D-values decreased from 1.153 to 0.791 ng/mL after chemotherapy compared with baseline. In the logistic regression analysis, the change of sPD-L1 levels in serum after chemotherapy were found to be a prognostic factor for treatment response and PFS in the multivariate analysis.ConclusionsThese results showed for the first time that sPD-L1 in serum samples of patients with advanced gastrointestinal cancer were changed after chemotherapy and increased serum sPD-L1 levels were poor prognostic factors for both tumor response and PFS of patients. Dynamic monitoring of serum sPDL1 after treatment may be served as a potential predictor to treatment response in gastrointestinal cancer patients.

P-039 5-Fluorouracil Degradation Rate in Patients with Recurrent Gastrointestinal Cancer Treated with Metronomic Capecitabine

P-039 5-Fluorouracil Degradation Rate in Patients with Recurrent Gastrointestinal Cancer Treated with Metronomic Capecitabine

Phase I clinical trial of a five-peptide cancer vaccine combined with cyclophosphamide in advanced solid tumors

We designed a phase I trial to investigate the safety, immune responses and clinical benefits of a five-peptide cancer vaccine in combination with chemotherapy. Study subjects were patients positive for HLA-A2402 with locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer. Eighteen patients including nine cases of colorectal cancer were treated with escalating doses of cyclophosphamide 4days before vaccination. Five HLA-A2402-restricted, tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1 and MPHOSPH1 were injected weekly for 4weeks. Treatment was well tolerated without any adverse events above grade 3. Analysis of peripheral blood lymphocytes showed that the number of regulatory T cells dropped from baseline after administration of cyclophosphamide and confirmed that TAA-specific T cell responses were associated significantly with longer overall survival. This phase I clinical trial demonstrated safety and promising immune responses that correlated with vaccine-induced T-cell responses. Therefore, this approach warrants further clinical studies.

671P - Dose Finding Study of Oxaliplatin, Irinotecan, and S-1 for Patients with Metastatic or Recurrent Gastrointestinal Cancer

ABSTRACT Aim: To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined oxaliplatin, irinotecan and S-1 chemotherapy on metastatic or recurrent gastrointestinal (GI) cancer Methods: Oxaliplatin and irinotecan were administered intravenously on day 1 and S-1 was administered orally on days 1-7 of every 2-week cycle. The doses of oxaliplatin/irinotecan/S-1 in phase I study were level 1, 85/120/60 mg/m2; level 2, 85/120/80 mg/m2; level 3, 85/120/100 mg/m2; level 4, 85/150/100 mg/m2; level 5, 85/180/100 mg/m2. Treatment was repeated until disease progression, unacceptable toxicity, or for a maximum of 12 cycles. Results: Twenty-two patients were enrolled in this study between October 2012 and February 2014 (median age, 59). One of six patients at level 1, 3 and 4 developed dose-limiting toxicity (febrile neutropenia) and none of three at level 5 did during the first cycle. As the planned maximum dose did not reach the MTD, the dose used at level 5 was defined as RD. Nineteen patients were evaluated for response. Two complete responses, seven partial responses were noted, and the overall response rate was 47.7%. Conclusions: The triple combination of oxaliplatin, irinotecan, and S-1 showed satisfactory toxicity profile and modest clinical benefit in patient with advanced GI cancer. The RD of oxaliplatin, irinotecan, and S-1 were 85 mg/m2, 180 mg/m2, and 100 mg/m2 every two weeks. Disclosure: All authors have declared no conflicts of interest.

Frequency of HER2 expression of circulating tumour cells in patients with metastatic or recurrent gastrointestinal cancer

Background:The clinical significance of circulating tumour cell (CTC) detection in gastrointestinal (GI) cancer remains controversial and the molecular biological characteristics of CTCs are poorly understood.Methods:A total of 87 patients with metastatic or recurrent GI cancer were prospectively enrolled. Circulating tumour cells and their HER2 status were assessed using the CellSearch System.Results:Among the 62 CTC-positive cases, we found 22 discordant cases (35.5%). Among the HER2-negative primary tumours, 17 of 54 developed HER2-positive CTCs. Five of eight had HER2-negative CTCs among the HER2-positive primary tumours.Conclusion:The findings in the current study suggest that it is critical to evaluate the HER2 status of not only the primary tumour but also the CTCs because the metastasising tumour cells are the primary target of systemic therapy.

Correlation of psychosocial factors (PSF) before and throughout treatment with response to chemotherapy (CTx) in patients (pts) with advanced gastrointestinal (GI) cancers: Does psychosocial status predict tumor remission?

542 Background: CTx has shown to have a positive impact on improving or maintaining quality of life (QoL) in patients with advanced GI cancers. The role of PSF in relation to objective tumor response (OTR) to CTx is not well described yet. We thus evaluated the predictive value of pretreatment PSF on OTR as well as the continuous evaluation of PSF in regard to OTR throughout treatment. Methods: Eligible pts had metastatic or recurrent GI cancer and were about to receive first- and second-line palliative CTx. QoL, physical symptoms and PSF were assessed by the EORTC QLQ C30, the MSKCC-Symptom Assessment Scale (MSAS), and a modified Brief-COPE before treatment start and after discussing the results of the first follow up OTR assessment. OTR was either classified according to RECIST or using a remission based approach (RA), classifying response as any decrease in size, and no change or progression as non-response. Results: 50 pts (median age 61.8 years, ECOG 0/1/2 12%/62%/26%, 21 female, 40% colorectal, 28% biliopancreatic, 24% esophagogastric, 78% 1st line CTx) were enrolled. OTR was 32% partial response, 50% stable disease and 18% progressive disease according to RECIST, and 60% response vs. 40% non-response according to RA. Interestingly, patients responding (RECIST and RA) to CTx had better role/emotional/cognitive functioning, mental state, global distress index, active coping, positive reframing, and belief in control over their lives, and less acceptance of their disease before treatment. PSF significantly predicted response (RA) to CTx, even if adjusted for age, cancer type, and line of treatment (p&lt;0.05). During course of treatment, PSF remained largely unchanged in responders, whereas non-responders loose belief and confidence in control, safety and equity and tend to increased denial (RECIST and RA). Those findings were more pronounced using the RA classification than RECIST. Conclusions: Pretreatment PSF seem to have predictive value for response to CTx in GI cancer patients. PSF changes in non-responding patients may be an early indicator for the need for psychological support in this patient group.

1671P - Phase I Clinical Trial of Cancer Vaccine Combined with Chemotherapy Targeting both Tumor Antigen and Immune Tolerance Against Advanced Solid Tumors

ABSTRACT Background Antitumor immunotherapy to target tumor antigens and evade immune tolerance is considered reasonable and promising. However, no combined immunotherapy has been established. We designed a phase I trial of cancer vaccine combined with chemotherapy to investigate safety as the primary endpoint, and immune responses and clinical benefits as secondary endpoints. Methods Patients positive for HLA-A2402 who showed locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer were evaluated in a phase I clinical trial of cancer vaccine and chemotherapy. Cyclophosphamide (CPM) was administered 4 days before vaccination to eliminate regulatory T cells (Treg). 18 patients were treated in cohorts of six patients, each with escalating CPM dose (150, 300 and 600 mg/m2). Five HLA-A2402-restricted tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1, and MPHOSPH1 were injected once a week for 4 weeks. Patients without gastrointestinal bleeding, pleural effusion or ascites also received low dose IL-2 every after vaccination. Results The treatment was tolerated well without any associated adverse events above grade 3. The study included primary disease with 9 cases of colorectal cancer, 3 cholangiocellular carcinoma, 3 lung cancer, and one each of esophageal, gastric and cervical cancer. Nine of 13 patients (69%) assessed by Elispot assay showed cytotoxic T lymphocytes (CTL) specific for TAA to more than one of five antigens after vaccination. Log-rank test among these demonstrated that CTL responses induced by vaccine contributed significantly to overall survival (MST: 9.2 vs 3.9 months, P = 0.003). In addition, a significantly broader antigenic repertoire was found in longer survivors (p = 0.033). Treg number dropped from baseline with dose just after CPM administration. This seems to reflect direct inhibition of CPM on Treg. Interestingly, reduced Treg correlated significantly with longer overall survival (P = 0.024), suggesting CPM augmented, vaccine-induced CTL responses through Treg reduction. Conclusion This phase I clinical study demonstrated promising survival associated with Treg inhibition, as well as CTL responses that warrants further clinical studies. Disclosure K. Yoshida: I am a research staff of the company, OncoTherapy Science Inc. providing the peptide vaccines used in this study. T. Tsunoda: I am the President and CEO of the company, OncoTherapy Science, Inc. providing the peptide vaccines used in this study. Y. Nakamura: I am one of the major stock holders of the company, OncoTherapy Science, Inc. K. Tani: Our department obtained the partial research funding in 2007 from the comapany, OncoTherapy Science, Inc. All other authors have declared no conflicts of interest.

化学療法併用活性化自己リンパ球移入療法が有効であった再発消化器癌の３例

当科では，活性化自己リンパ球移入療法をがんに対する免疫療法として導入してきた．しかし，単独では抗腫瘍効果を得ることは困難で，化学療法を併用する症例が多い．本稿では，この化学療法併用リンパ球療法が有効であった再発消化器癌の３例を報告する．症例１は44歳，女性．StageⅣ胃癌に対して胃全摘術を施行し，病理学組織学的にCY1であった．術後化学療法が有害事象により不可能で，リンパ球療法を開始した．４年半後に腹膜転移が出現し，低用量化学療法も併用した．その４年後，腹膜転移が増悪したため再手術を施行し，その後再び治療を継続して腹膜転移は制御されている．症例２は77歳，女性．StageⅢA胃癌に対して根治手術施行．リンパ節転移が出現したため化学療法併用リンパ球療法を施行し，リンパ節転移はCRとなっている．症例３は63歳，女性．大腸癌術後肝転移再発に対して化学療法併用リンパ球療法を施行し，肝転移について長期間CRが得られている．

Phase I clinical trial of hybrid cell vaccination in patients with gastrointestinal cancer

2579 Background: Vaccination with hybrid cells of dendritic cells (DCs) and tumor cells can induce specific ant-tumor immunity against multiple tumor antigens including those that are unknown. We report the results of phase I study of hybrid cell vaccines comprised of autologous DC and autologous tumor cells in patients with Stage IV or recurrent gastrointestinal cancer. Method: Thirteen patients with Stage IV or recurrent gastrointestinal cancer were enrolled in this study after informed consent was obtained. Tumor cells were cryopreserved following acquisition from the primary or a metastatic site. DCs were induced from mononuclear cells of patients by culture with cytokines (6 days culture with GM-CSF and IL-4, and a further 1 day culture with TNF-α, IL-1 β, IL-6 and PGE2). Fusion of irradiated tumor cells and DC was created with a combination of PEG and electrofusion (two-step fusion method). At 2 week interval, patients received 4 freshly prepared fusion vaccines, with a constant dose range of 1 × 107 to 4 × 107 cells. The endpoints of this study were assessments of safety, anti-tumor immune response and clinical response. Results: Serious adverse events were not observed in any of the enrolled patients and all Common Toxicity Criteria were grade I. Clinical responses are 1 with partial response (PR), 5 with stable disease (SD) and 7 with progressive disease (PD). Delayed skin tests changed to positive in 5 patients. In patients with PR and SD, a shift to Th1 in Th1/Th2 balance of lymphocytes (IFN γ/IL10, IFN γ/IL4) was demonstrated by ELISPOT and cytokine flow cytometry analysis. After vaccination, decrease of immunosuppressive factors (IAP, TGF-β) in serum were shown in patients with PR and SD. There was no significant differences of CD4+CD25+ cells by vaccination. Conclusion: These results suggests that a strategy of hybrid cell vaccine employing auto-DCs and auto-tumor cells is feasible in patients with gastrointestinal cancer and may show evidence of anti-tumor immune response. No significant financial relationships to disclose.

A phase I study of immunotherapy with tumor cell-dendritic cell fusion vaccine in patients with advanced or recurrent gastrointestinal cancer

2615 Background: Immunotherapy with tumor cell-dendritic cell fusion vaccine has been shown to induce the immune response against multiple tumor antigens including unknown tumor antigens. The aim of this study was to test safety, feasibility, and clinical response of immunotherapy with tumor cell-dendritic cell fusion vaccine. Methods: Nine patients with advanced or recurrent gastrointestinal cancer that is unresponsive to standard surgical therapy and chemotherapy were enrolled in this study after informed consent was obtained. Monocytes were separated from the peripheral blood by leukapheresis and were cultured with GM-CSF and IL-4 for 6 days. Then TNFα, IL-1β, IL-6, and PGE2 were added for maturation of dendritic cells. Fusion of irradiated tumor cells and dendritic cells was created by polyethylene glycol and electroporation. Fusion vaccine was subcutaneously injected in the inguinal region four times every two weeks. Safety and adverse effects were evaluated after vaccination. Delayed hypersensitivity skin-test, cytokine array, Th1/Th2, Tc1/Tc2, and clinical response were compared before and after vaccination. Results: There were neither adverse effects nor autoimmune responses after vaccination in all the patients. Delayed skin tests became positive in six of nine patients after vaccination. Th1/Th2 balance and Tc1/Tc2 balance were improved in six of nine patients after vaccination. IAP levels were decreased in five patients after vaccination. Clinical response was stable disease in five patients and progressive disease in four patients. Conclusions: Safety and feasibility of immunotherapy with tumor cell-dendritic cell fusion vaccine were confirmed in patients with advanced or recurrent gastrointestinal cancer by this study. No significant financial relationships to disclose.

A phase I study of immunotherapy with tumor cell-dendritic cell fusion vaccine in patients with advanced or recurrent gastrointestinal cancer

2615 Background: Immunotherapy with tumor cell-dendritic cell fusion vaccine has been shown to induce the immune response against multiple tumor antigens including unknown tumor antigens. The aim of this study was to test safety, feasibility, and clinical response of immunotherapy with tumor cell-dendritic cell fusion vaccine. Methods: Nine patients with advanced or recurrent gastrointestinal cancer that is unresponsive to standard surgical therapy and chemotherapy were enrolled in this study after informed consent was obtained. Monocytes were separated from the peripheral blood by leukapheresis and were cultured with GM-CSF and IL-4 for 6 days. Then TNFα, IL-1β, IL-6, and PGE2 were added for maturation of dendritic cells. Fusion of irradiated tumor cells and dendritic cells was created by polyethylene glycol and electroporation. Fusion vaccine was subcutaneously injected in the inguinal region four times every two weeks. Safety and adverse effects were evaluated after vaccination. Delayed hypersensitivity skin-test, cytokine array, Th1/Th2, Tc1/Tc2, and clinical response were compared before and after vaccination. Results: There were neither adverse effects nor autoimmune responses after vaccination in all the patients. Delayed skin tests became positive in six of nine patients after vaccination. Th1/Th2 balance and Tc1/Tc2 balance were improved in six of nine patients after vaccination. IAP levels were decreased in five patients after vaccination. Clinical response was stable disease in five patients and progressive disease in four patients. Conclusions: Safety and feasibility of immunotherapy with tumor cell-dendritic cell fusion vaccine were confirmed in patients with advanced or recurrent gastrointestinal cancer by this study. No significant financial relationships to disclose.

Repeated immune cell transfer therapy combined with non myeloablative chemotherapy in patients with refractory recurrent gastrointestinal and lung cancer

Repeated immune cell transfer therapy combined with non myeloablative chemotherapy in patients with refractory recurrent gastrointestinal and lung cancer

Repeated immune cell transfer therapy combined with non myeloablative chemotherapy in patients with refractory recurrent gastrointestinal and lung cancer

2541 Background: Autologous tumor cells stimulated T lymphocytes (AuTL) were generated ex vivo from peripheral blood lymphocytes (PBL) over a two week co-culturing process and they may have potential for efficacy as a cellular immunotherapy (IT) in refractory gastrointestinal and lung cancer patients (pts). We investigated the feasibility of a combination of AuTL transfer and chemotherapy (ChT) with S1or ZD1839 (Iressa) conditioning regimen in order to take advantage by both the anticancer and lymphodepleted effects for reconstruction of antitumor immune followed by AuTL transfer as well as an adoptive IT. Method: 13 patients were enrolled in a pilot clinical trial. The two administrations of AuTL were given prior to one ChT for one treatment cycle. The treatment was repeated at least three cycles with a one-week interval. The nonmyeloablative ChT regimen was based on standard dose of S-1 for pts with gastric (4 pts), colon (4 pts) or esophageal (3 pts) cancer and of ZD1839 for 2 pts with lung adenocarcin...

Intraoperative radiotherapy for gastrointestinal cancer.

Local recurrence following potentially curative tumor resection is a major problem in patients with gastrointestinal cancer. To augment surgical excision and to avoid the disadvantages of external beam irradiation, intraoperative radiotherapy (IORT) has been applied to primary and recurrent gastrointestinal cancer, both with curative intent and for palliation. There is ample evidence that the combination of radical surgery and IORT can improve local control. Whether this eventually can translate into improved overall survival has not yet been studied in adequately powered randomized and controlled trials.

Pilot study of continuous-infusion 5-fluorouracil, oral leucovorin, and upper-abdominal radiation therapy in patients with locally advanced residual or recurrent upper gastrointestinal or extrapelvic colon cancer

Purpose : The purpose of this study was to develop a satisfactorily tolerated regimen of radiation therapy, continuous infusion 5-fluorouracil, and leucovorin in patients with locally advanced upper-abdominal gastrointestinal cancer. Methods and Materials : Patients with locally advanced or locally recurrent gastric, pancreatic, or extrapelvic colon cancer were eligible for this study. Radiation therapy consisted of 45 Gy in 25 fractions to the tumor and regional lymph nodes, followed by 5.4–9 Gy in three to five fractions to the tumor. Treatment with leucovorin, 10 mg orally daily, and continuous infusion 5-fluorouracil was initiated on the first day of radiation therapy. 5-Fluorouracil was administered at an initial daily dose of 125 mg/m 2, with dose escalation planned in 25-mg increments, depending on patient tolerance. Results : Twenty-one evaluable patients participated in this study. Six were treated at the initial daily 5-fluorouracil dose of 125 mg/m 2. One patient experienced Grade 4 anorexia and nausea. No other Grade ≤3 toxicity was observed at this dose. Fifteen evaluable patients were entered at a planned 5-fluorouracil dose of 150 mg/m 2 daily; 6 of them experienced Grade 3 toxicity, and none experienced Grade ≤4 toxicity. Grade 3 toxicities and the number of patients who developed each were: vomiting (three patients); nausea (two patients); diarrhea (two patients); and skin toxicity, hand-foot syndrome, catheter-related infection, and stomatitis in one patient each. Four of the six patients who experienced Grade 3 toxicity developed more than one type of Grade 3 toxicity. Conclusion : In patients with upper-abdominal gastrointestinalc ancer, continuous infusion 5-fluorouracil (150 mg/m 2 daily), leucovorin (10 mg orally daily), and radiation therapy (50–54 Gy) resulted in a 40% rate of severe toxicity but no life-threatening toxicity. This clinical trial excludes, with 90% confidence, a 20% risk of Grade 4 toxicity with this combination. The 40% rate of severe toxicity suggests that this combination of agents is near the maximal tolerated dose.