Prognostic factor analysis in third-line chemotherapy for elderly patients with metastatic gastric cancer.

82 Background: Recently, the proportion of elderly patients (pts) with metastatic gastric cancer (mGC) has increased in Japan. Survival benefits of salvage treatment after second-line chemotherapy (CTX) for mGC were shown in several prospective studies. However, the role of salvage treatment in elderly pts remains controversial. Methods: We reviewed 185 pts with mGC who received palliative CTX aged ≥ 70 years at our institution between April 2007 and March 2018. Eligibility criteria were as follows: PS 0-2, refractory to first-line and second-line CTX. The purpose of this study was to evaluate the clinicopathologic factors that affected overall survival for elderly pts with mGC, univariate and multivariate analyses were performed on the baseline factors at the beginning of third-line CTX. Results: Of all, 71 pts were eligible. Median age was 75 years (71-85). Median progression-free survival (PFS) and overall survival (OS) for third-line CTX were 3.2 and 7.5 months, respectively and an overall response rate and disease control rate were 4.2% and 43.7%, respectively. In univariate analysis, the following four factors were identified to have prognostic significance: performance status (PS) (ECOG 0–1 or 2), serum albumin level (< 3.5 or ≥ 3.5 g/dl), serum LDH level (≤ 240 or > 240 IU/l), PFS under second-line CTX (< 3 or ≥ 3 months). Multivariate analysis found three prognostic factors affecting poor survival following third-line CTX: PS of 2 (hazard ratio (HR) 8.89, 95% confidence interval (CI) 3.99–20.2; P = 0.001), serum LDH level > 240 IU/l (HR 2.75, 95% CI 1.48–5.05; P = 0.002) and median PFS under second-line CTX of < 3 months (HR 1.89, 95% CI 1.01–3.43; P = 0.045). A prognostic index was constructed, dividing pts into low- (0 factor), intermediate- (1-2 risk factors), or high- (3 risk factors) risk groups. Median OS for each group were 12.6, 6.0 and 3.0 months, respectively ( P < 0.001). Conclusions: This analysis suggests that some clinicopathologic factors might be helpful in identifying the subgroup of elderly pts most likely to benefit from third-line CTX for metastatic gastric cancer.

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Efficacy and prognostic factor analysis in second-line chemotherapy for elderly patients with metastatic gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.143 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 143-143

Author(s):

Ayaka Shoji ◽

Hiroko Hasegawa ◽

Seiya Kato ◽

Ryosuke Kiyota ◽

Kazuma Shinkai ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factors ◽

Elderly Patients ◽

Progression Free Survival ◽

Metastatic Gastric Cancer ◽

The Other ◽

Second Line ◽

Eligibility Criteria ◽

Second Line Chemotherapy ◽

Line Chemotherapy

143 Background: Recently, the proportion of elderly patients (pts) with advanced gastric cancer has increased in Japan. Survival benefits of second-line chemotherapy (CTX) such as weekly paclitaxel (PTX)±Ramucirumab (RAM) or irinotecan (CPT) were shown in several phase 3 trials for metastatic gastric cancer (mGC). However, efficacy and prognostic factors in the second line CTX for elderly pts are not well studied. Methods: We retrospectively reviewed for mGC pts aged ≥ 70 years who underwent PTX+RAM, PTX or CPT as second-line CTX. Eligibility criteria were as follows: PS 0-2, refractory to an S-1containing CTX. Response rate (RR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Univariate and multivariate analyses were performed to determine prognostic factors of survival. Results: There were 250 pts with mGC treated at our institution between April 2007 and March 2017. Of all, total of 85 pts were eligible. Median age was 75 years (71-85). The RR was 28.0% in the PTX+RAM group (n=28), 17.2% in the PTX group (n=29) and 18.5% in the CPT group (n=28). Median PFS was 5.1 months(M) and MST was 12.2 M in the PTX+RAM group, compared with 4.1 M and 9.7 M in the PTX group, or 3.3M and 9.8M in the CPT group. The ORR, PFS and OS were better in the PTX+RAM group though differences between groups were not statistically significant. Grade 3 or higher non-hematological AEs such as fatigue or diarrhea were more frequent in the CPT group on the other hand, hematological AEs were more frequent in the PTX+RAM group. On multivariate analysis, PS (HR,3.13; 95%CI, 1.60-5.77), LDH (HR,3.19; 95%CI, 1.80-5.57), and CEA (HR,2.35; 95%CI, 1.30-4.16) were found to be significant prognostic factors for elderly pts with mGC who underwent second-line CTX. Conclusions: PTX+RAM therapy seemed to be more effective than the other regimens. Furthermore, this analysis for prognostic factors may help clinicians to better select elderly pts who may benefit from a second-line CTX.

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Second-line chemotherapy in advanced gastric cancer: A retrospective, single-center analysis

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15170 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15170-15170

Author(s):

C. Herrmann ◽

D. Jaeger ◽

T. Herrmann

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Advanced Gastric Cancer ◽

Chemotherapy Regimen ◽

Salvage Chemotherapy ◽

Second Line ◽

First Line ◽

Second Line Chemotherapy ◽

Third Line ◽

Line Chemotherapy

15170 Background: The role of second-line chemotherapy in advanced gastric cancer is not yet established. We analyzed patients with advanced gastric cancer treated at our department between 2002 and 2005 comparing the outcome of patients with first-line chemotherapy only and those who received second-line chemotherapy. Patients and Methods: 51 patients with metastatic or recurrent histologically confirmed gastric cancer were analyzed in this retrospective study. The choice of chemotherapy depended on the attending physician. Results: Altogether, 17 patients (33.3 %) were treated with only one chemotherapy regimen, whereas 34 patients (66.6 %) received at least two different chemotherapy regimens. During the last years, the preference for certain chemotherapy regimens changed. At the time of analysis, 9 patients were still alive. Median overall survival was 11 months (range: 1–41). Patients who received only one chemotherapy regimen were older (median age 70, range: 47–81), had a shorter TTP (3.5 months, range: 1–15) and a shorter overall survival (6 months, range: 2–25) than patients receiving sequential chemotherapies (median age 61.5 (range: 33–79) p = 0,009, TTP under first-line therapy 5 months (1–17), p = 0,45, overall survival 14.5 months (2–41), p = 0,001). Response to second-line chemotherapy was assessed in 32 patients: Partial remission was detected in 4 patients (12.5 %), stable disease for = 3 months in 15 patients (46.8 %), whereas disease progression occurred in 12 patients (37.5 %). 10 of 51 patients (19.6 %) received more than two different treatments: 4 patients had third-line chemotherapy, 6 patients had more than 3 different therapies. Overall survival was 13 months (11–22) for patients with third-line chemotherapy and 29 months (16–41) for patients receiving more than three different treatment regimens. Conclusion: Although a number of active antineoplastic drugs are available for the treatment of advanced gastric cancer, the prognosis is still poor. Selected patients may benefit from salvage chemotherapy after failure of first-line chemotherapy. No significant financial relationships to disclose.

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Multicenter randomized phase II study of weekly docetaxel alone versus weekly docetaxel plus oxaliplatin as a second-line chemotherapy in patients with advanced gastric cancer: Preliminary response and safety results.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14570 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14570-e14570 ◽

Cited By ~ 2

Author(s):

Jin Young Kim ◽

Young Rok Do ◽

Keon Uk Park ◽

Hun-Mo Ryoo ◽

Sung Hwa Bae ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Advanced Gastric Cancer ◽

Therapy Group ◽

Progression Free Survival ◽

Combination Group ◽

Second Line ◽

Free Survival ◽

Weekly Docetaxel ◽

Line Chemotherapy

e14570 Background: Gastric cancer is a frequent malignancy with worldwide estimated incidence of 990,000 cases, representing 7.8% of all cancers in 2008. There are limited data suggesting a benefit for doublet second-line chemotherapy in advanced gastric cancer. Methods: The eligibility criteria were patients 1) with prior exposure to cisplatin based chemotherapy and advanced or recurrent stomach cancer 2) with pathologically proven gastric adenocarcinoma, 3) with an ECOG performance status 0 to 2, 4) with measurable lesions. Each treatment cycle was consisted of docetaxel 36 mg/m2 in docetaxel mono therapy group and docetaxel 36 mg/m2, oxaliplatin 80 mg/m2 in docetaxel/oxaliplatin doublet therapy group on days 1, 8. The primary end point of this study was response rate, and secondary end points included toxicity, progression free and overall survival. Results: Fifty two patients were enrolled; median age was 63 years; male (n=42) and female (n=10); docetaxel mono therapy (n=27) and docetaxel/oxalliplatin doublet therapy (n=25). The median number of cycles administered was 2.5 (range,1-9). Fourty eight patients were assessable for efficacy. Four partial responses, 7 stable diseases in mono therapy group (RR; 4/27, 14.8%) and 1 complete remission, 4 partial responses, 13 stable diseases in double therapy group (RR; 5/25, 20.0%) were confirmed (p=0.198). Median progression free survival was 1.97 months in the mono therapy group and 4.93 months in doublet therapy group (p=0.007). Median overall survival was 11.57 months in the mono therapy group and 8.13 months in doublet therapy group (p=0.650). Grade 3 or 4 adverse events were reported in 11 of 52 patients; G3 pain were in 2 patients and G3 pneumonia was in 1 patient in mono group, G3/4 neutropenia were 5 patients in the combination group, G3 nausea, vomiting, general weakness was 1 patient each group in combination group. Conclusions: Weekly docetaxel/oxaliplatin doublet therapy showed superior progression free survival to monotherapy group as second line therapy in cisplatin pretreated advanced gastric cancer patients.

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Correlation between overall survival and other endpoints in clinical trials of second-line chemotherapy for patients with advanced gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.4067 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 4067-4067

Author(s):

Kohei Shitara ◽

Keitaro Matsuo ◽

Kei Muro ◽

Atsushi Ohtsu

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Advanced Gastric Cancer ◽

Rank Correlation ◽

Progression Free Survival ◽

Second Line ◽

Second Line Chemotherapy ◽

Randomized Studies ◽

Low Correlation ◽

Line Chemotherapy

4067 Background: The correlation between progression-free survival (PFS) or time to progression (TTP) and overall survival (OS) has been evaluated in patients with advanced gastric cancer (AGC) who received first-line chemotherapy (Shitara, K et al. Invest New Drug 2011; Shitara K and Burzykowski T, et al, ASCO 2011). However, no corresponding analysis had been done in patients who underwent second-line chemotherapy for AGC. Methods: We evaluated the potential of PFS, TTP, response rate (RR), or disease control rate (DCR) to act as surrogates for OS in phase II and III trials of second-line chemotherapy for AGC by comprehensive literature-based analysis. Correlations between each endpoint and OS were evaluated by Spearman rank correlation coefficient (ρ). Subgroup analyses by trial region or type of failure to previous chemotherapy were also conducted. Results: Fifty-six trials, including four randomized studies, were selected for analysis and covered a total of 61 treatment arms and 3,038 patients; 34 studies were conducted in Asia, 20 studies in Non-Asian countries, and two studies in both regions. Median PFS were similar in Asian and Non-Asian trials (3.0 vs. 3.3 months). In contrast, median OS tended to be longer in Asian vs. Non-Asian trials (8.0 vs. 6.0 months; p<0.01). Median PFS/TTP and OS showed a moderate correlation with ρ of 0.51 (95% CI, 0.31-0.73). Correlation tended to be higher in PFS (ρ = 0.62) than TTP (ρ = 0.29) and higher in non-Asian trials (ρ = 0.73) than Asian trials (ρ = 0.32). Correlation between PFS/TTP and OS among the trials in which eligibility required failure to previous fluorouracil and cisplatin also showed low correlation (ρ = 0.48). The RR and DCR also did not show high correlation with OS (ρ = 0.30 for RR; 95% CI 0.04-0.56; ρ = 0.53 for DCR; 95% CI 0.31-0.75). The hazard ratio (HR) of PFS and OS in each arms of the four randomized studies showed a low correlation with ρ of 0.10. Conclusions: Our results indicate that PFS/TTP, RR, and DCR did not correlate sufficiently with OS to be used as surrogate endpoints in patients with AGC who underwent second-line chemotherapy. Further research is needed based on individual patient data from ongoing randomized trials.

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Tumor angiogenesis genotyping and efficacy of first-line chemotherapy in metastatic gastric cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.64 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 64-64

Author(s):

Mario Scartozzi ◽

Riccardo Giampieri ◽

Cristian Loretelli ◽

Alessandro Bittoni ◽

Alessandra Mandolesi ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Metastatic Gastric Cancer ◽

Second Line ◽

Tumour Angiogenesis ◽

First Line ◽

Altered Expression ◽

Second Line Chemotherapy ◽

Gastric Cancer Patients ◽

Line Chemotherapy

64 Background: An altered expression of tumour angiogenesis-related factors has been constantly associated to a more aggressive phenotype and an increased relapse rate in several tumour types, including gastric cancer. Besides correlating with prognosis, tumour-driven angiogenesis seemed also able to influence response/resistance to chemotherapy in pre-clinical models. We examined the role of tumour angiogenesis genotyping in determining clinical outcome in metastatic gastric cancer patients receiving first-line chemotherapy. Methods: VEGF-A, VEGF-C, FLT1, KDR and FLT4 genotyping was performed on gastric tumours from 94 consecutive patients receiving platinum-based first-line chemotherapy. Results: Only theVEGF A rs25648 correlated with RR (PR = 18% among patients showing the VEGF A rs25648 CT or TT genotype vs. 44% among patients showing the VEGF A rs25648 CC genotype, p = 0.04). The VEGF A (rs2010963) and VEGF C (rs4604600 and rs7664413) correlated with mPFS and the VEGF A rs25648 and FLT4 rs307833 correlated with both mPFS and OS. Among other clinical variables tested (sex, age, ECOG performance status, gastrectomy, adjuvant chemotherapy, metastatic sites and second-line chemotherapy) only the use of second-line chemotherapy correlated with improved overall survival (10.2 months vs. 6.3 months for patients who received or did not receive second-line, p= 0.003). At multivariate the VEGF A rs25648 maintained an independent role in determining both median PFS (HR = 1.65 95% CI: 1.12-2.78, p= < 0.0001) and OS (HR = 1.58, 95% CI: 1.17-2.65, p = 0.0003). The use of second-line chemotherapy also showed an independent role in determining median OS (HR = 0.58, 95% CI: 0.38-0.87, p= 0.003). Conclusions: VEGF A rs25648 genotyping may help identifying a patients subgroup unlikely to benefit from a first-line, platinum-based combination and potentially candidate to alternative therapy choices. Our data may help designing future clinical trials with the aim to investigate the outcome of different chemotherapy regimens in different patients groups prospectively stratified according to angiogenesis profile.

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Optimal indications for palliative chemotherapy in elderly patients with metastatic or recurrent gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.207 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 207-207

Author(s):

Hiroko Hasegawa ◽

Kazumasa Fujitani ◽

Aya Sugimoto ◽

Shoichi Nakazuru ◽

Motohiro Hirao ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Elderly Patients ◽

Primary Tumor ◽

Multivariate Analyses ◽

Performance Status ◽

First Line ◽

Recurrent Gastric Cancer ◽

Significant Difference ◽

Line Chemotherapy

207 Background: Gastric cancer is the second causes of cancer-related deaths in the world and its incidence of advanced gastric cancer (AGC) in the elderly is increasing as a result of increased life expectancy. However, elderly patients have been underrepresented in many kinds of chemotherapy clinical trials. Therefore it is difficult to evaluate the efficacy and safety of chemotherapy for elderly patients and select the appropriate patients aged 70 years or older who are likely to benefit from the chemotherapy. Methods: There were 265 patients with primary unresectable or recurrent gastric cancer treated at our institution between April 2007 and March 2014. Of all, 90 patients aged 70 years or older were retrospectively identified. We evaluated the efficacy of the chemotherapy and prognostic significance of clinico-pathologic factors to identify the optimal indications for chemotherapy. Univariate and multivariate analyses were perfomed on the base-line characteristics such as patient’s performance status (PS), gender, chemotherapy regimens, history of gastrectomy, presense of co-morbidity, serum LDH level, serum C reactive protein, and nutritional status, at the initiation of the first-line chemotherapy. Results: The median overall survival time (OS) was 343 days and the median TTF on first-line chemotherapy was 111 days. The toxicity was mild and tolerable. There were no significant difference in overall survival between patients receiving monotherapy and combination therapy. On multivariate analyses, PS 1 or 2 (hazard ratio (HR), 1.883; 95% confidence interval (CI), 1.047–3.390), presence of primary tumor (HR, 1.916; 95% CI, 1.063–3.448) at the initiation of the first- line chemotherapy were identified as significant independent poor prognostic factors for overall survival. Especially in patients aged 75 years or older, only PS was an independent prognostic factor for OS (HR, 3.703; 95% CI, 1.314–9.900). Conclusions: Analysis of our results shows that patients aged 70 years or older with good performance status and absence of primary tumor might achieve clinical benefit from chemotherapy.

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