Metastatic Adenocarcinoma Of Stomach Research Articles

A Prospective Study to Evaluate the Efficacy of the Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel Chemotherapy Regimen in Patients with Locally Advanced and Metastatic Adenocarcinoma of Stomach

Abstract Introduction In India, patients with gastric cancer present at an advanced stage, and there is no standard chemotherapy regimen. Al-Batran's fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy gave us a glimmer of hope. Objectives Hence, we intended to evaluate the efficacy of FLOT chemotherapy in locally advanced and metastatic adenocarcinoma of stomach. Materials and Methods In this single-center, prospective cohort, patients with locally advanced and metastatic gastric adenocarcinoma who required chemotherapy between March 2016 and November 2017 were included in the study. All patients received standard FLOT chemotherapy. The primary objective was to evaluate the safety and efficacy of FLOT chemotherapy in the Indian population. Overall survival (OS) and progression-free survival (PFS) were calculated through the plotted Kaplan–Meier curves. Results In our study, 28 patients received FLOT chemotherapy. Their mean age was 55 years (range, 28–70 years) with a male preponderance (89.3%). Twenty-five patients had metastatic disease (89.3%), and three had locally advanced disease (10.7%). The median number of cycles was 4.5 (range, 1–8), and 75% received at least four cycles (n = 21). The hematological toxicities exhibited were neutropenia (50%) and febrile neutropenia (35.7%). Sixteen (57.1%) patients needed dose modifications due to treatment-related adverse effects (AEs). AEs led to treatment discontinuation in seven (25%) patients after the first cycle. The overall response rate in the intent-to-treat population was 52.7%, with the best-obtained response being a partial response, median PFS of 5 months, and median OS of 13 months. Conclusion FLOT chemotherapy regimens induced excellent responses but with significantly increased toxicity, needing dose modifications, and hence, should be considered only in a young and fit patient.

Effectiveness and Safety of Apatinib in Patients with Advanced or Metastatic Adenocarcinoma of Stomach or Gastroesophageal Junction: A Prospective Observation Study.

BackgroundApatinib showed promising efficacy in the treatment of advanced or metastatic gastric cancer (mGC) in previous clinical studies. However, the real-world data are limited, and this study aimed to assess the effectiveness and safety of apatinib for the treatment of advanced or mGC in this setting.MethodsIn this prospective observational study, progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR) and treatment-related adverse events (AEs) were recorded and evaluated. Univariate and multivariate analyses were conducted to explore potential biomarkers which might be related to the effectiveness.ResultsA total of 321 mGC patients from 47 centers in China were enrolled between July 1, 2015, and March 1, 2018. Thirty-two patients achieved partial response, 155 patients achieved stable disease, and 115 patients had progressive disease, and no CR was achieved, illustrating an ORR of 10.60% and a DCR of 61.92%. The median PFS and OS were 4.0 and 8.2 months, respectively. Multivariate Cox analysis showed that the potential biomarkers associated with longer PFS were combination regimens plus taxel/docetaxel, and apatinib initial dosage ≥500mg, occurrence of AEs of leukopenia, and hand-foot syndrome. Main AEs were proteinuria (17.1%), hypertension (15.9%), and handfoot syndrome (8.7%).ConclusionThe present prospective observational study showed favorable effectiveness and safety of apatinib in real-world patients with advanced or metastatic GC in China. (A prospective, multi-center, non-intervention study of apatinib in the treatment of advanced gastric cancer-Trial Registry Number: ChiCTR-OPN-15006601).

Dose-finding study of modified FLOT (mFLOT) regimen as first-line treatment in Chinese patients with metastatic adenocarcinoma of stomach.

To determine the maximum tolerated dose (MTD) and recommended dose (RD) of modified FLOT regimen (fluorouracil plus leucovorin, oxaliplatin and docetaxel) for treating Chinese patients with metastatic adenocarcinoma of stomach. Chinese patients with untreated advanced or metastatic stomach adenocarcinoma were enrolled. Docetaxel (D), oxaliplatin (O) and leucovorin were administrated intravenously on day 1. Fluorouracil (F) was administrated continuous intravenously on day 1 for 48h. The treatment was repeated every 2weeks. The start doses of docetaxel and oxaliplatin were 40mg/m2 and 65mg/m2, respectively. Dose escalation followed a 3 + 3 design. Total 6 dose levels were set to determine the MTD and RD. Fluorouracil and leucovorin were given as fix doses at 2200mg/m2 and 200mg/m2, respectively. Adverse events that occurred in the first 2 cycles were recorded to determine dose-limiting toxicity (DLT). The primary endpoints were MTD and RD determination. A total of 18 patients were treated in 5 dose levels. DTL occurred in one patient of level 4 (grade 3 hypophosphatemia). Other 3 patients were enrolled in level 4 and no DLTs were observed. In level 5, 2 patients suffered grade 4 neutropenia after first cycle of treatment and were defined as DLTs. Therefore, level 5 (D/O/F: 50/75/2200mg/m2) was defined as MTD and level 4 (D/O/F: 45/75/2200mg/m2) was defined as RD. Common adverse events in first two cycles were nausea, anorexia, leukopenia, neutropenia and anemia. For 16 patients assessable for tumor response, 7 patients had partial response (43.7%) and 5 experienced stable disease. Disease control rate were 75% (12/16). Two patients underwent conversion operation after 6 cycles of treatment. One pathological complete response (case in level 3) and one pathological partial response (case in level 2) were observed. Median progression-free survival was 4.4months (95% CI 2.9-5.9months) in 14 patients. The RD of modified FLOT regimen in Chinese patients with advanced gastric cancer was docetaxel 45mg/m2, oxaliplatin 75mg/m2, leucovorin 200mg/m2 and fluorouracil 2200mg/m2 on day 1 of every 14-day cycle. Its efficacy will be assessed by further phase II study.

Association of proteinuria, hypertension, and hand-foot-skin reaction with efficacy of apatinib in gastric cancer: Results from the post-marketing study (Ahead-G201).

73 Background: Ahead-G201 is an ongoing open-label, multicenter, post-marketing Phase IV trial assessing safety and efficacy of apatinib in 2000+ patients (pts) with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction. Proteinuria (PTN), hypertension (HTN) and hand-foot-skin reaction (HFSR) are common adverse events (AEs) related to anti-angiogenesis drugs. Methods: As of 2017/7/10, 1037 and 820 pts were evaluable for safety and survival. Clinical outcomes were compared between pts with and without PTN / PTN / HFSR using Kaplan–Meier methods and multivariate Cox regression model. Results: 200 (19.3%), 194 (18.8%) and 115 (11.1%) pts had PTN, HTN and HFSR, respectively. Similar mean daily dosage was found between pts with and without PTN, HTN or HFSR (from 520.6 to 551.0 mg/day). Pts developed PTN / HTN / HFSR had longer median medication durations (57 vs. 33 / 55 vs. 35 / 65 vs. 36 days; p<0.001). However, there was no significant difference in tumor response and progression free survival (PFS) between pts with and without PTN/HTN/HFSR (Table). Only pts had HFSR showed significantly longer overall survival (OS) (8.38 vs. 5.95 months; p=0.0003). After adjusted for baseline and treatment characteristics, presence of HFSR was found to be independently associated with prolonged OS (HR: 1.82 [95%CI, 1.25–2.66]). Conclusions: Occurrence of HFSR is an independent predictor of better OS. Prior analysis based on Phase II and III indicated the relationship between HTN and prolonged OS, which needs to be further analyzed. Clinical trial information: NCT02426034. [Table: see text]

Comparisons between intestinal and diffuse gastric cancer in response to apatinib: Data from post-marketing phase IV study.

36 Background: Intestinal and diffuse gastric cancer are main histological types of gastric cancer, based on Lauren’s classification, which account for 34–47% and 46–57%, respectively. Patients (pts) with intestinal gastric cancer have better prognosis. The present study aimed to compare the safety and efficacy of apatinib between the two intestinal gastric cancer, based on data from post-marketing Phase IV study (Ahead-G201). Methods: The single-arm, open-label, multi-center, Phase IV trial enrolled advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction after failure of ≥2 lines of chemotherapy. Data of pts with intestinal and diffuse gastric cancer were collected and compared. Results: As of 2017/7/10, 96 intestinal and 104 diffuse pts were recruited. Differences in age (64 vs. 55 yrs), gender (male: 77.1% vs. 57.7%) and disease duration ( > 12 months: 71.3% vs. 56.7%) were detected. Between intestinal and diffuse gastric cancer, there was no discrepancy in incidences of adverse events (AEs) (78.1% vs. 73.1%) and Grade ≥3 AEs (41.7% vs. 38.5%). The incidences of typical AEs associated anti-angiogenesis drugs were also comparable (hypertension 26.0% vs. 16.4%; proteinuria 14.6% vs. 20.2%; hand-foot-skin reaction 16.7% vs. 9.6%). No statistical difference was observed in best overall response rate (12.8% vs. 14.3%) and disease control rate (76.0% vs. 64.3%). Survival benefit in pts with intestinal gastric cancer was detected (progression free survival: 5.52 vs. 2.76 months, p = 0.036; overall survival: 8.11 vs. 4.70 months, p = 0.047). However, the multivariable Cox regression model analysis showed that histological type was not independently prognostic factors for survival, indicating that clinical benefit of pts with intestinal gastric cancer was influenced by other factors. Conclusions: Compared with diffuse gastric cancer, pts intestinal gastric cancer have more clinical benefit after treated by apatinib. However, histological type based on the Lauren’s classification was not independently prognostic factors for survival, which needs to be further analyzed, considering the small sample size. Clinical trial information: NCT02426034.

Effects of apatinib dose interruptions on safety and efficacy in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction in third- or later-line setting.

142 Background: Apatinib, a small molecule VEGFR TKI, has been approved in the treatment of advanced gastric cancer in China. Due to toxicity, many pts underwent temporary interruptions during treatment. We analyzed the data from a phase IV clinical trial of Ahead-G201 to evaluate the relationship between dose interruption, drug safety and efficacy. Methods: At the cutoff date of Jul 10, 2017, Ahead-G201 study enrolled 1037 pts. The adverse events (AEs) and clinical efficacy were evaluated for pts with no, 1, 2 and ≥3 dose interruptions. Results: 336 of 1037 pts underwent dose interruptions during apatinib treatment: 1 interruption in 183 pts; 2 interruptions in 67 pts; and ≥3 interruptions in 86 pts. The toxicity and efficacy for them were listed in Table. For safety, pts with no interruption had the lowest incidence of all AEs (59.3%) and grade 3-4 AEs (30.0%). Pts with ≥3 interruptions had the highest objective response rate (ORR, 20.3%) and disease control rate (DCR, 82.6%). Moreover, these pts got median progression-free survival (mPFS) of 6.6 mos and median overall survival (mOS) of 9.4 mos, which were the longest among 4 groups. Furthermore, multivariate analysis revealed that ≥3 interruptions of apatinib bring much more efficacy benefit both in mPFS (6.6 vs 3.8 mos: hazard ratio, 0.5, 95%CI, 0.3 to 0.7) and mOS (9.4 vs 6.6 mos: hazard ratio, 0.5, 95%CI, 0.3 to 0.8) for pts, than those with no interruption. Conclusions: Current results indicated that dose interruptions are required to manage toxicity and it is necessary to explore an optimal dosing pattern of apatinib in advanced gastric cancer. Clinical trial information: NCT02426034. [Table: see text]

Initial dose of apatinib in Chinese patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction in third- or later-line setting: 500 mg or 850 mg?

35 Background: A fine balance between maintaining efficacy and reducing toxicity is necessary for drug therapies in many cancers. This study seeks to review the data from phase IV clinical trial of Ahead-G201 to help elucidate the optimal initial dose of apatinib in advanced gastric cancer. Methods: Pts data from the Ahead-G201 study at cut-off date of Jul 10, 2017 were extracted to explore the correlation of apatinib initial dose (500 mg vs 850 mg) with safety and clinical efficacy. Results: 864 of eligible pts received apatinib at an initial dose of 500 mg, and 58 pts received at 850 mg. Dose interruption occurred in 258 pts (33.1%) at 500 mg and in 27 pts (46.5%) at 850 mg. For safety, the most common adverse events (AEs) were proteinuria, hypertension and leukocyte decrease in both groups. Moreover, the incidence of all AEs and grade 3-4 AEs in pts at 500 mg was significantly lower than pts at 850 mg (Table). For efficacy, pts at 500 mg achieved an objective response rate (ORR) of 10.8% and a disease control rate (DCR) of 70.6%, at best response, which were 10.3% and 55.2% in pts at 850 mg. Pts at 500 mg got a significantly longer median progression-free survival (mPFS) and median overall survival (mOS) than pts at 850 mg (PFS, 4.6 mos vs 2.2 mos; OS, 6.8 mos vs 4.0 mos). Multivariate analysis indicated that apatinib treatment at an initial dose of 500 mg was significantly associated with longer mOS in advanced gastric cancer pts (6.8 mos vs 4.0 mos: hazard ratio, 0.5; 95%CI, 0.3 to 0.8), compared to initial dose of 850 mg. Conclusions: Compared to receiving apatinib at initial dose of 850mg, oral administration of apatinib starting from 500 mg seemed to bring more clinical benefit for patients with advanced gastric cancer, whilst with lower toxicities. Clinical trial information: NCT02426034. [Table: see text]

Effect of region and hospital attribute on outcome of gastric patients treated with apatinib: Data from post-marketing phase IV study.

40 Background: The single-arm, open-label, multi-center, Phase IV trial of apatinib was conducting in patients (pts) with advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction with a target sample size of 2000+. We aimed to analyze the effect of region and hospital attributes on clinical outcomes. Methods: From April 2015 to July 2017, 1037 subjects were enrolled, among which 820 were evaluable in the survival analysis. Results: The incidences of adverse events (AEs) and severe AEs (SAEs) are listed in Table. Overall, both incidences were higher in Southern center compared to Northern Center (p=0.002 and <0.001). More SAEs occurred in developed cities (p=0.028) and in hospitals not specialized in oncology (p=0.028). For efficacy, the median overall survival (mOS) of subjects in Northern Center and Southern centers were 8.71 and 5.72 mos (p<0.001), and the median progression free survival (mPFS) was 5.36 and 3.25 mos (p=0.002), respectively. The mOS of subjects in developed and developing cities were 6.18 and 5.72 mos (p=0.105), and the mPFS was 3.02 and 4.73 mos (p=0.013), respectively. The mOS of subjects in hospital specialized and those not in oncology were 7.59 and 5.78 mos (p=0.014), and the mPFS was 4.73 and 3.84 mos (p=0.068), respectively. Conclusions: Region and attribute hospital can affect the safety and clinical outcome of apatinib in treating gastric cancer in the real world. Patients Northern, developing city or hospitals specialized in oncology experience less SAEs but have better clinical benefit. Clinical trial information: NCT02426034. [Table: see text]

Apatinib as third-line or beyond therapy in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction: An open-label, multicenter, post-marketing phase IV study (Ahead-G201).

103 Background: The clinical benefit and safety profile of apatinib in advanced gastric cancer have been established in the randomised controlled phase III clinical trial (J Clin Oncol. 34(13):1448-54). A post-marketing study to confirm the safety and efficacy of apatinib is ongoing in a broad range of patients (pts). Methods: This is a single-arm, open-label, multi-center, Phase IV trial with the target sample size of 2000+ (ClinicalTrials.gov Identifier: NCT02426034). Pts were recruited to receive oral apatinib until disease progression, death or unacceptable toxicity. The primary objective was safety, and the secondary objectives included overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Results: Herein, we report the preliminary data as documented in the EDC System. As of Jul 10, 2017, 1037 pts were enrolled from 138 hospitals across China. Pts characteristics were: median age 59 yrs, male/female 72.0/28.0%, ECOG PS 0/1/≥2 16.6/66.2/17.2%, stage IV 91.0%. 336 (32.4%) pts interrupted treatment and dose modification occurred in 172 (16.6%) pts (reduction 132/12.7%; rise 87/8.4%). Eventually, the mean dosage was 526.2 mg/d. 652 (62.9%) pts had 4407 drug-related adverse events (DRAEs). Grade ≥3 DRAEs occurred in 300 (28.9%) pts. Severe AEs were reported by 221 (21.3%) pts. The most common DRAEs were proteinuria (19.3%), hypertension (18.8%), leukocyte decrease (16.4%), fatigue (14.2%), platelet decrease (13.6%), hand-foot-skin reaction (11.1%) and neutrophil decrease (10.1%). 820 pts were evaluable for efficacy analysis. The best ORR and DCR were 10.7% and 70.0%, respectively. The median PFS and OS were 4.60 (95%CI, 3.25–4.73) and 6.57 (95%CI, 5.78–7.59) months, respectively. Conclusions: Apatinib monotherapy is effective and has a favorable toxicity profile in real-world clinical setting. The preliminary results of this Phase IV study confirmed the safety and efficacy of apatinib demonstrated in the Phase II and III trials. Updated results will be discussed. Clinical trial information: NCT02426034.

Krukenberg Tumor from Gastric Carcinoma presented as Acute Abdomen: A Unique Presentation

ABSTRACT Krukenberg tumor is an ovarian metastatic tumor from the digestive tract accounting for 10% of all ovarian malignancies. The uniqueness of this tumor is its morphology disguising as the primary tumor. We present a case of gastric carcinoma in a 36-year-old woman, who presented as acute abdomen to the emergency department. Abdominal examination revealed tender, cystic to firm mass of size 14 × 10 × 8 cm in the left lower quadrant. The abdominal ultrasonography revealed the ovarian mass of the above-mentioned size with minimal free fluid in the peritoneal cavity. An explorative laparotomy disclosed bilateral ovarian masses. Histological findings of both ovarian masses were consistent with metastatic adenocarcinoma of stomach. The survival rate of the patients can be improved by tumor-free surgery and a novel platinum-based chemotherapy. Krukenberg tumor should be considered in differential diagnosis of acute abdomen. How to cite this article Jarathi A, Ramamoorthy S, Mohan J. Krukenberg Tumor from Gastric Carcinoma presented as Acute Abdomen: A Unique Presentation. J South Asian Feder Menopause Soc 2017;5(1):66-68.

Erythropoetin (epoetin beta) once weekly in anemic patients with advanced cancer of the stomach or gastroesophageal junction: Interim results of a randomized German AIO phase II trail

15133 Background: Tumor-related or chemotherapy-induced anemia is common in gastrointestinal cancer patients and results in reduced quality of life and worse prognosis. Thus, the effectiveness of erythropoetin (epoetin beta) treatment (EB) to achieve and maintain a target haemoglobin (Hb) level of ≥ 11 g/dl was assessed within a randomised German AIO phase II study to assess efficacy of irinotecan/capecitabine versus cisplatin/capecitabine in advanced gastric or lower esophageal cancer. Methods: Patients (pts) with untreated locally advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction (KPS ≥ 60%, > one measurable lesion, adequate organ functions) were randomized to receive 3-weekly cycles of either irinotecan 250 mg/m2 d1 (arm A) or cisplatin 80 mg/m2 d1 (arm B). Capecitabine was administered at 2000 mg/m2 for 14 days in both arms. In both arms, EB (30,000 I.E. once weekly) was given at Hb of < 11 g/dl and continued until Hb ≥ 12 g/dl. If after 4 treatment weeks, Hb increase was < 0.5 g/dl, EB was increased to 30,000 I.E. twice weekly. FACT-An questionnaires were completed at each cycle. Results: At time of abstract submission, 81 pts were randomized to A (37 pts) or B (44 pts). 23 pts received at least 3 EB injections (A: 10 pts, B: 13 pts). Median Hb prior to EB was 10.5 g/dl (A: 10.4 g/dl, B: 10.5 g/dl) and median Hb at end of EB was 11.6 g/dl (A: 11.5 g/dl, B: 11.75 g/dl). During EB, 80 % of A and 77 % of B achieved target Hb of ≥ 11 g/dl with a median rise in Hb of 2.0 g/dl (A: 1.4 g/dl, B: 2 g/dl). 5 pts in A and 7 pts in B responded with a ≥ 1 g/dl rise in Hb during first 4 weeks. FACT-An questionnaires showed no change from baseline to end of EB. Among evaluable pts with EB (20 pts) versus without EB (34 pts), response (CR + PR) and tumor control rates (CR + PR + SD) were 60% vs 35% and 85% vs 70%, respectively. Conclusions: EB is effective in raising Hb levels in advanced or metastatic gastric cancer. Patients receiving EB tend to show a better response to chemotherapy. No significant financial relationships to disclose.

Irinotecan/capecitabine versus cisplatin/capecitabine in advanced adenocarcinoma of the stomach or gastroesophageal junction: Interim analysis of a randomized German AIO phase II study

4032 Background: Irinotecan with 5-FU is highly effective in advanced gastric cancer. In addition, capecitabine seems to be as effective as 5-FU, with its advantage of oral administration. Thus, we compared efficacy and toxicity of irinotecan/capecitabine versus cisplatin/capecitabine in this prospective multicentric, open trail. Methods: Patients (pts) with previously untreated locally advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction and Karnofsky Performance status (KPS) of ≥ 60%, at least one measurable lesion and adequate organ functions were eligible. Pts were randomized to 3-weekly cycles of irinotecan 250 mg/m2, day 1 (arm A) or to cisplatin 80 mg/m2, day 1 (arm B). Capecitabine was administered at a 1000 mg/m2 twice daily for 14 days followed by a 7-day rest in both arms. Primary endpoint was remission rate, treatment was continued until disease progression. Results: At time of abstract submission, 91 of 120 pts (planned sample size) were randomized to arm A (45 pts) or B (46 pts). Interim data were available on 76 patients included into intent to treat analysis (34 pts arm A, 42 pts arm B). Baseline characteristics (arm A vs. B) were median age: 60 vs. 64 years, gender (female/male) 23%/77% vs. 30%/70%, KPS (≥80%) 97% vs. 93%, tumor distribution of gastric origin and gastroesophageal junction 85%/15% vs. 63%/37%. Grade 3 toxicities in A/B (% of pts) were anemia 3/9, neutropenia 17/19, diarrhoea 17/5, nausea 14/21, vomiting 3/14, hand-foot syndrome 6/2, respectively. Grade 4 toxicity occured only for neutropenia with 3% vs.5% in A/B, respectively. In 59 evaluable pts (28/31 in A/B), overall remission rate (CR + PR) and tumor control rate (CR + PR + SD) were 39% vs. 42% and 64% vs. 74%, respectively. Despite being only very descriptive, median progression-free and overall survival (arm A vs B) were 5.2 vs. 5.0 and 8.9 vs. 9.4 months, respectively. Conclusions: In patients with locally advanced or metastatic gastric and gastroesophageal cancer, both regimen irinotecan/capecitabine or cisplatin/capecitabine are effective, well tolerated and can be administered safely on an out-patient basis. Currently, both treatment arms are comparable. Accrual continues. No significant financial relationships to disclose.