Background
Some clinicopathological variables are known to influence the survival of patients with advanced gastric cancer. A comprehensive model based on these factors is needed for prediction of an ...individual’s survival and appropriate patient counseling.
Methods
A nomogram for predicting 1-year survival in patients with advanced gastric cancer in the palliative chemotherapy setting was developed using clinicopathological data from 949 patients with unresectable or metastatic gastric cancer who had received first-line doublet cytotoxic chemotherapy from 2001 to 2006 at the National Cancer Center, Korea (Baseline Nomogram). For 836 patients whose initial response to chemotherapy is known, another nomogram (ChemoResponse-based Nomogram) was constructed using the response to chemotherapy as additional variable. Nomogram performance in terms of discrimination and calibration ability was evaluated using the
C
statistic and Hosmer–Lemeshow-type
χ
2
statistics.
Results
Two different nomograms were developed and subjected to internal validation. The baseline nomogram incorporated 13 baseline clinicopathological variables, whereas the chemoresponse-based nomogram was composed of 11 variables including initial response to chemotherapy. Internal validation revealed good performance of the two nomograms in discrimination:
C
statistics = 0.656 (95% confidence interval, 0.628–0.673) for the baseline and 0.718 (95% confidence interval, 0.694–0.741) for the chemoresponse-based nomogram, which showed significantly better discrimination performance than the baseline nomogram (
Z
statistics = 3.74,
p
< 0.01).
Conclusion
This study suggests that individual 1-year survival probability of patients receiving first-line doublet cytotoxic chemotherapy for advanced gastric cancer can be reliably predicted by a nomogram-based method incorporating clinicopathological variables and initial response to chemotherapy.
Background Self-expandable metallic stents (SEMSs) provide effective palliation of malignant pyloric obstruction in patients with inoperable gastric cancer. Objective To compare the effectiveness and ...side effects of covered and uncovered SEMSs for the palliation of malignant pyloric obstruction. Design Prospective, randomized, single-center study. Setting Tertiary-care cancer center hospital. Patients This study involved 80 patients with pyloric obstruction related to inoperable gastric cancer. Intervention Covered or uncovered SEMS placement. Main Outcome Measurements Technical and clinical success rates as well as the patency rate at 8 weeks after placement. Results Both groups had a technical success rate of 100% with no immediate complications. Both groups also had comparable clinical success rates (covered SEMS, 95% 38 of 40 and uncovered SEMS, 90% 36 of 40, P = .68) and 8-week patency rates (covered SEMS, 61.3% 19 of 31 and uncovered SEMS, 61.1% 22 of 36, P > .99). Stent migration within 8 weeks was more common in the covered SEMS group (25.8% 8 of 31) than in the uncovered SEMS group (2.8% 1 of 36, P = .009), whereas re-stenosis because of tumor ingrowth was more common in the uncovered SEMS group (25.0% 9 of 36 vs 0% 0 of 31 in the covered SEMS group, P = .003). Overall patient survival and stent patency did not differ between groups ( P = .27 and 0.61 by log-rank test, respectively). Limitations The study population was limited to gastric cancer patients, and stent designs were changed in the midst of the study period. Conclusion Both the covered and uncovered SEMSs are effective and have comparable 8-week patency in patients with malignant pyloric obstruction, despite different patterns of late stent failure.
Countries differ in their treatment expertise and research results regarding gastric cancer; hence, treatment guidelines are diverse based on evidence and medical situations. A comprehensive and ...comparative review of each country's guidelines is imperative to understand the similarities and differences among countries. We reviewed and compared five gastric cancer treatment guidelines in terms of endoscopic, surgical, perioperative, and palliative systemic treatment based on evidence levels and recommendation grades, as well as the postoperative follow-up strategies for each guideline. The Korean, Chinese, and European guidelines provided evidence and grading of the recommendations. The United States guidelines suggested categories for evidence and consensus. The Japanese guidelines suggested evidence and recommendations only for systemic treatment. The Korean and Japanese guidelines described endoscopic treatment, surgery, and lymphadenectomy in detail. The Chinese, United States, and European guidelines more intensively considered perioperative chemotherapy. In particular, the indications for chemotherapy and the regimens recommended by each guideline differed slightly. Considering their medical situations, each guideline had some diversity in terms of adopting evidence, which resulted in heterogeneous recommendations. This review will help medical personnel to comprehensively understand the diversity in gastric cancer treatment guidelines for each country in terms of evidence and recommendations.
We compared continuous versus stop-and-go chemotherapy after disease stabilisation with induction chemotherapy in the first-line treatment of metastatic gastric cancer (MGC).
MGC patients who ...achieved disease control after 6 cycles of S-1/oxaliplatin (SOX) were randomised to receive either continuous SOX until progression (continuous arm) or to have a chemotherapy-free interval followed by SOX reintroduction at progression (stop-and-go arm). The primary end-point was overall survival (OS).
Of the 250 patients enrolled, 247 participated in the induction phase. Of these, 121 patients were randomised to the continuous arm (n = 59) or the stop-and-go arm (n = 62). Progression-free survival (PFS) was significantly longer in the continuous arm than in the stop-and-go arm (10.5 versus 7.2 months; hazard ratio HR 0.55, 95% CI, 0.37–0.81; P = 0.002). Duration of disease control (DDC) and OS, however, were comparable between the two arms: median DDC, 10.5 versus 11.3 months, HR 0.92 (95% CI, 0.62–1.36; P = 0.674); median OS, 22.6 versus 22.7 months, HR 0.78 (95% CI, 0.50–1.23; P = 0.284). Adverse events including grade ≥3 fatigue (28.8% versus 8.1%; P = 0.003) and sensory neuropathy (25.4% versus 9.7%; P = 0.022) occurred more frequently in the continuous arm than in the stop-and-go arm. Quality of life (QOL) including global health status, physical/role functioning and other symptom scores significantly favoured the stop-and-go arm.
Compared with the stop-and-go strategy, maintenance chemotherapy improved PFS but not DDC and OS and had a negative impact on QOL, suggesting the stop-and-go strategy may be an appropriate option in MGC patients following induction chemotherapy.
•Duration of first-line chemotherapy is addressed in metastatic gastric cancer.•Continuous chemotherapy prolongs progression-free survival but not overall survival.•The stop-and-go strategy has favourable adverse events and quality of life profiles.•The stop-and-go strategy is a reasonable option following induction chemotherapy.
Background
In this post hoc analysis of the PRODIGY study, we aimed to investigate factors associated with survival outcomes and provide evidence for designing optimal perioperative treatment ...strategies for gastric cancer patients receiving neoadjuvant chemotherapy.
Patients and methods
A total of 212 patients in the neoadjuvant chemotherapy group of the PRODIGY study were included as the study population. The prognostic impact of clinicopathologic factors, including the initial radiological clinical stage (cStage) and post-neoadjuvant chemotherapy pathological stage (ypStage), was analyzed.
Results
The median age was 58 years. The majority of patients (77.4%) had cStage III disease, and about 10% and 25% had ypStage 0 and I disease, respectively. According to the initial cStage, progression-free survival (PFS) and overall survival (OS) were significantly different (
P
< 0.01). PFS and OS were also different according to the ypStage (
P
< 0.01). In multivariate analyses, cStage IIIC disease (vs. cStage II) and ypStage II and III disease (vs. ypStage 0/I) were independent factors for poor survival outcomes. Based on the patterns of PFS and OS according to both cStage and ypStage, three patient groups were defined. These groups showed distinct PFS and OS (
P
< 0.01) with 5-year PFS rates of 95.7%, 77.9%, and 31.3% and 5-year OS rates of 95.7%, 82.4%, and 42.5%, respectively.
Conclusions
Both initial cStage and ypStage were independent factors for survival outcomes of gastric cancer patients treated with neoadjuvant chemotherapy. Efforts should be made to develop optimal peri-operative treatment strategies for patients at different risks according to cStage and ypStage.
Background
We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to investigate the association between
...CYP2A6
genotype and outcome.
Methods
Patients with LAGC clinical stage III–IV (M0) by the Japanese staging system received three cycles of pre- and postoperative chemotherapy (S-1 40 mg/m
2
twice daily on days 1–14; intravenous docetaxel 35 mg/m
2
on days 1 and 8, every 3 weeks) followed by gastrectomy with D2 dissection. We also performed a pharmacokinetic and
CYP2A6
genotyping study (
*1
,
*4
,
*7
,
*9
,
*10
) for S-1.
Results
From October 2006 to June 2008, 44 patients entered the study. 43 eligible patients completed preoperative chemotherapy and 40 completed postoperative chemotherapy. The most common G3/4 toxicities during pre- and postoperative chemotherapy were neutropenia, stomatitis, and abdominal pain. The clinical response rate by RECIST was 74.4 % (95 % CI, 61.4–87.4 %), and the R0 resection rate was 97.7 %. Clinical downstaging in T or N occurred in 41.9 % of patients. The 3-year progression-free survival (PFS) rate was 62.8 % and 5-year overall survival (OS) rate was 69.6 %. PFS and OS differed significantly according to clinical response, clinical downstaging, and
CYP2A6
genotype. Patients with
CYP2A6
variant/variant genotypes had a higher tegafur
C
max
and worse survival than those with wild/wild or wild/variant genotypes.
Conclusion
Perioperative S-1 plus docetaxel is active with a manageable toxicity in patients with LAGC receiving D2 surgery. Clinical tumor response, clinical downstaging, and
CYP2A6
genotype may predict efficacy.
S‐1 is an oral 5‐fluorouracil agent containing tegafur, 5‐chloro‐2, 4‐dihydroxypyridine (CDHP), and potassium oxonate. This study explored the pharmacokinetics of S‐1 and pharmacokinetic changes ...after gastric surgery in patients with resectable gastric cancer who received pre‐ and postoperative S‐1 plus docetaxel. Serial blood was drawn before and after gastrectomy from 37 patients for pharmacokinetic analysis. The pharmacokinetics of tegafur, 5‐fluorouracil, and CDHP were analyzed by noncompartmental analysis (NCA) methods and by modeling. In modeling analysis, CHDP concentrations were incorporated in the model as a time‐varying covariate that inhibits the clearance of 5‐fluorouracil following an inhibitory Emax model. In NCA, the pharmacokinetics of tegafur and 5‐FU before and after gastric surgery were similar, although average maximum concentrations of 5‐FU were decreased with statistical significance after gastrectomy. Median Tmax of tegafur was shorter after surgery without statistical significance. In modeling analysis, tegafur was best fitted by mixed zero and first‐order absorption. The only difference in the final pharmacokinetic model around gastrectomy was the presence of an absorption lag of 0.23 hours before surgery. Incorporation of CDHP concentrations significantly improved the model. Although some pharmacokinetic results showed statistically significant changes after gastrectomy, these differences seem to be too small to have any clinical implication.
Background
In this randomized phase II study, we evaluated the efficacy and safety of sorafenib in combination with capecitabine and cisplatin (XP) as first‐line chemotherapy in advanced gastric ...cancer.
Patients and Methods
Patients with metastatic gastric or gastroesophageal junction adenocarcinoma were randomized (1:1) to receive either sorafenib plus XP (S + XP) or XP alone. In cases of disease progression in the XP arm, crossover to sorafenib alone was allowed. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included overall survival (OS), response rates, safety profiles, and biomarkers, and the response rates and PFS with secondline sorafenib alone after progression in the XP arm.
Results
Between Jan 2011 and Feb 2013, a total of 195 patients were accrued (97 in the S + XP arm and 98 in the XP alone arm). The overall response rate was 54% with S + XP, and 52% with XP alone (p = 0.83). With a median follow‐up of 12.6 months (range, 0.1–29.2), the median PFS assessed by independent review was 5.6 months in the S + XP arm and 5.3 months in the XP arm (hazard ratio HR 0.92, 95% confidence interval CI 0.67–1.27, p = 0.61). Overall survival was not different between the two arms (median 11.7 vs. 10.8 months; HR 0.93, 95% CI 0.65–1.31, p = 0.66). Frequencies of grade 3/4 toxicities were similar between the S + XP and XP alone arms, except for neutropenia (21% vs. 37%), anorexia (0% vs. 5%), and hand‐foot skin reaction (7% vs. 1%). Among 51 patients who crossed over to sorafenib alone after disease progression in the XP arm, there was no objective response and their median PFS was 1.3 months (95% CI, 1.2–1.7).
Conclusion
The addition of sorafenib to XP chemotherapy was safe but not more effective than XP alone for first‐line treatment of metastatic gastric cancer.
In this randomized phase II study, we evaluated the efficacy and safety of sorafenib in combination with capecitabine and cisplatin (XP) as first‐line chemotherapy in advanced gastric cancer. The combination of sorafenib and XP was feasible and well tolerated, but it did not show any differences in efficacy outcomes compared with standard XP. Further investigation of this combination regimen is not warranted in GC, at least in the first‐line setting, if patients are not selected by definite biomarkers.
It has been reported that the survival of patients with locally advanced gastric cancer (LAGC) is better in East Asia countries than in developed western countries; however, the prognosis of LAGC ...remains poor. This study aimed to evaluate the effects of perioperative chemotherapy on the long-term survival of East Asia patients with LAGC.
From October 2006 through August 2008, 43 patients with LAGC received perioperative S-1 combined with weekly docetaxel in a phase II study (neoadjuvant group). These patients were matched using propensity scores to patients who underwent surgery without neoadjuvant chemotherapy during the same period (surgery group). The surgical outcomes and long-term survivals were compared between the 2 groups.
After matching, 43 and 86 patients were included in the neoadjuvant and surgery groups, respectively, and there was no significant difference in their baseline characteristics. Although the operating time was longer in the neoadjuvant group, there was no significant difference in postoperative complications between the 2 groups. The neoadjuvant group had a significantly higher 5-year overall survival (OS) rate (73.3% vs. 51.1%, P=0.005) and a trend towards higher 5-year progression-free survival (PFS) (62.8% vs. 49.9%, P=0.145). In the multivariate analysis, perioperative chemotherapy was an independent factor for OS, with a hazard ratio of 0.4 (P=0.005) and a marginal effect on the PFS (P=0.054).
Perioperative chemotherapy was associated with better long-term survival without increasing postoperative complications in the setting of D2 surgery for patients with LAGC, suggesting that perioperative chemotherapy can be a therapeutic option in East Asia countries.
Purpose We performed a retrospective study to evaluate the efficacy of cetuximab plus chemotherapy in metastatic gastric cancer (MGC) patients previously treated with chemotherapy and to investigate ...potential predictors of treatment efficacy in those patients. Methods Thirty-two patients with MGC were included in this study. Cetuximab was delivered, often combined with irinotecan-based chemotherapy. Thirty patients were analyzed for K-ras mutations via direct sequencing of the tumor DNA. Results Patients were heavily pretreated with a median number of three previous lines of palliative chemotherapy (56% of the patients were refractory to all of the following drugs: fluoropyrimidines, cisplatin, irinotecan, oxaliplatin, and docetaxel) and 53% of the patients displayed poor performance status. Of 28 response-assessable patients, the overall response rate to cetuximab plus chemotherapy was 3.6% 95% confidence interval (CI) 0-10.5% and the disease control rate was 28.6%. The median progression-free survival (PFS) was 1.7 months (95% CI 1.3-2.1 months), and the median overall survival (OS) was 3.2 months (95% CI 1.4-5.0 months). Multivariate analyses revealed that skin rash and performance status were significantly associated with PFS and OS. The presence of a K-ras mutation (13.3%) was not associated with either PFS or OS. Conclusion Our study suggests that MGC patients with good performance status and skin rash benefit most from salvage cetuximab combined with chemotherapy, even in heavily pretreated status.
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