First-line bolus 5-fluorouracil plus leucovorin for peritoneally disseminated gastric cancer with massive ascites or inadequate oral intake

Hara, Hiroki; Kadowaki, Shigenori; Asayama, Masako; Ooki, Akira; Yamada, Teppei; Yoshii, Takako; Yamaguchi, Kensei

doi:10.1007/s10147-017-1198-7

Cited by 24 publications

(32 citation statements)

References 22 publications

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“…However, GC usually shows resistance to chemotherapeutics which exhibit a relatively short control of this disease and correlated symptoms, and the survival of most of these patients is less than one year [ 9 , 10 ]. Furthermore, the application of chemotherapy often produces adverse events such as fatigue, nausea, pancytopenia, and significant gastrointestinal toxicity [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Network Pharmacology‐Based Approach to Investigate the Mechanisms of Hedyotis diffusa Willd. in the Treatment of Gastric Cancer

Liu

Zhang

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Background Hedyotis diffusa Willd. (HDW) is one of the renowned herbs often used in the treatment of gastric cancer (GC). However, its curative mechanism has not been fully elucidated. Objective To systematically investigate the mechanisms of HDW in GC. Methods A network pharmacology approach mainly comprising target prediction, network construction, and module analysis was adopted in this study. Results A total of 353 targets of the 32 bioactive compounds in HDW were obtained. The network analysis showed that CA isoenzymes, p53, PIK3CA, CDK2, P27Kip1, cyclin D1, cyclin B1, cyclin A2, AKT1, BCL2, MAPK1, and VEGFA were identified as key targets of HDW in the treatment of GC. The functional enrichment analysis indicated that HDW probably produced the therapeutic effects against GC by synergistically regulating many biological pathways, such as nucleotide excision repair, apoptosis, cell cycle, PI3K/AKT/mTOR signaling pathway, VEGF signaling pathway, and Ras signaling pathway. Conclusions This study holistically illuminates the fact that the pharmacological mechanisms of HDW in GC might be strongly associated with its synergic modulation of apoptosis, cell cycle, differentiation, proliferation, migration, invasion, and angiogenesis.

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Section: Introductionmentioning

confidence: 99%

Network Pharmacology‐Based Approach to Investigate the Mechanisms of Hedyotis diffusa Willd. in the Treatment of Gastric Cancer

Liu

Zhang

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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“…Unfortunately, most pivotal phase III trials have not included patients with AGC who present with SPM; hence, the standard first-and second-line chemotherapy for such patients has not been established to date [2][3][4][5]12]. Some retrospective studies have shown the efficacy and safety of fluoropyrimidine-based regimen as first-line chemotherapy for patients with AGC who present with SPM [9][10]13].…”

Section: Discussionmentioning

confidence: 99%

Second-line chemotherapy using taxane in patients with advanced gastric cancer who presented with severe peritoneal metastasis: A multicenter retrospective study

Arai

Kawahira

Yasui

et al. 2019

Preprint

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Background Individuals with advanced gastric cancer (AGC) who present with severe peritoneal metastasis (SPM) have poor prognosis, and the need to improve treatment for such condition and survival time is not met. Moreover, there are only few data about the second-line treatment for patients with such condition. Methods This retrospective study included patients receiving taxane-based second-line chemotherapy at three institutions in Japan between 2010 and 2016. Patients with AGC who present with SPM were included if they had massive ascites and/or inadequate oral intake requiring intravenous nutritional support. The efficacy and safety of the treatment were evaluated. Results In the present study, 43 (40%) of 108 patients had an Eastern Cooperative Oncology Group Performance Status score > 2, and the median serum albumin level of the patients was 3.3 g/mL. Ramucirumab was used in combination with paclitaxel in 21 patients. The median overall survival (OS) and progression-free survival (PFS) were 5.1 and 2.8 months, respectively. Inadequate oral intake was considered a negative prognostic factor of both OS and PFS in the multivariate analysis. Three treatment-related deaths were observed, which include those attributed to febrile neutropenia, gastrointestinal perforation, and pneumonitis. Common grade > 3 adverse events were neutropenia (35%), leukopenia (30%), anemia (24%), and anorexia (16%). We observed febrile neutropenia in 8% and gastrointestinal perforation in 4% of patients, and such conditions were primarily observed in patients with inadequate oral intake. Conclusions Taxane-based second-line chemotherapy was effective and safe for patients with AGC who present with SPM. Attention must be provided when treating patients with inadequate oral intake as they are likely to have short prognosis and serious toxicities.

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“…Numerous regimens have been investigated, with median survival times of patients in mostly small single-arm studies of systemic chemotherapy ranging between 5.2 and 18 months [66]. Clinical trial data from recent retrospective analyses have shown improvements in ascites following systemic chemotherapy in patients with AGC, including in patients with massive ascites [17,18,67,70]. As patients with massive ascites have few treatment options, are more likely to start treatment on a reduced dose, and may miss the opportunity to receive second-line treatment because of failure of first-line treatment followed by rapid disease progression, it is particularly important to optimize the efficacy of firstline treatment in this patient population [17,18].…”

Section: Clinical Trial Datamentioning

confidence: 99%

“…Clinical trial data from recent retrospective analyses have shown improvements in ascites following systemic chemotherapy in patients with AGC, including in patients with massive ascites [17,18,67,70]. As patients with massive ascites have few treatment options, are more likely to start treatment on a reduced dose, and may miss the opportunity to receive second-line treatment because of failure of first-line treatment followed by rapid disease progression, it is particularly important to optimize the efficacy of firstline treatment in this patient population [17,18]. Recently, a phase 2/3 study (JCOG1108/WJOG7312G) of chemotherapy in patients with AGC, severe peritoneal metastases, and massive ascites, reported that sequential treatment was feasible [71].…”

Section: Clinical Trial Datamentioning

confidence: 99%

“…Because of poor PS, elderly patients and patients with massive ascites may not be considered for a subsequent line(s) of treatment, particularly because these patients have decreased organ function and comorbidities and, therefore, are at greater risk of toxicity and complications [14][15][16][17][18]. Good patient management will likely play an important role in sequential therapy by minimizing the adverse effects of treatment while maximizing the benefits.…”

Section: Introductionmentioning

confidence: 99%

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Achieving sequential therapy in advanced gastric cancer: the importance of appropriate patient management for the elderly and/or those with ascites

2020

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Treatment options for patients with advanced gastric cancer (AGC) are limited. One approach to improving survival in patients with AGC is to optimize the available agents via sequential therapy. However, clinical trial reports of first-line chemotherapy indicate that elderly patients and patients with massive ascites are less likely to receive subsequent lines of therapy. In addition, clinical trials of second-and third-line chemotherapy generally exclude these two patient populations because they are likely to have poor performance status and additional issues that are difficult to manage. Good patient management is likely to be key to the successful use of sequential therapy in these two patient populations by minimizing adverse effects to allow patients to derive benefit from the additional treatment. This narrative review summarizes the available information on AGC treatment and patient management in elderly patients and patients with massive ascites. The available data suggest that elderly patients benefit from chemotherapy; however, monitoring toxicity is essential to avoid chemotherapy-related toxicities. Important aspects of patient management for elderly patients include symptom monitoring, nutritional support, and fall prevention. The available data for patients with massive ascites show limited success for a range of treatment approaches, including systemic chemotherapy. The management of ascites is also challenging, with no clear guidance on the preferred strategies. To address these gaps in knowledge, future clinical trials should incorporate more inclusive eligibility criteria to enroll populations of patients with AGC that are more reflective of the real-world population with respect to age, complications, and overall health status.

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First-line bolus 5-fluorouracil plus leucovorin for peritoneally disseminated gastric cancer with massive ascites or inadequate oral intake

Abstract: Our study suggests that bolus 5-FU plus l-leucovorin therapy is feasible and has clinical activity as palliative therapy in patients with severe peritoneal metastases from gastric cancer.

Cited by 24 publications

References 22 publications

Network Pharmacology‐Based Approach to Investigate the Mechanisms of Hedyotis diffusa Willd. in the Treatment of Gastric Cancer

Network Pharmacology‐Based Approach to Investigate the Mechanisms of Hedyotis diffusa Willd. in the Treatment of Gastric Cancer

Second-line chemotherapy using taxane in patients with advanced gastric cancer who presented with severe peritoneal metastasis: A multicenter retrospective study

Achieving sequential therapy in advanced gastric cancer: the importance of appropriate patient management for the elderly and/or those with ascites

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