Gastric%20cancer Treatment

Treatment

Supportive Therapy

Should be considered in patients with stage IV disease that can improve survival compared with best supportive care alone
- Co-morbidities, organ function and performance status must always be taken into consideration
Decision to offer palliative or best supportive care alone or in combination with systemic therapy is based on the patient's performance status

Chemoradiation

May be an option for medically fit patients with locally unresectable tumors and have no previous therapy
Preferred regimens include:
- Cisplatin and Fluorouracil
- Cisplatin and Capecitabine
- FOLFOX
- CAPOX
Other recommended regimens include: Fluoropyrimidine (Fluorouracil or Capecitabine) and Paclitaxel

Systemic Therapy

Provides palliation of symptoms, enhances quality of life and improves survival of patients with locally advanced or metastatic gastric cancer

First-line Therapy

Two-drug cytotoxic combination regimens are preferred due to lower toxicity
Three-drug cytotoxic combination regimens are reserved for medically fit patients with good performance status
Oxaliplatin is preferred over Cisplatin due to lower toxicity
Preferred regimens for HER2 overexpression-positive adenocarcinoma include:
- Fluoropyrimidine (5-FU or Capecitabine) and Cisplatin and Trastuzumab
- Fluoropyrimidine (5-FU or Capecitabine) and Oxaliplatin and Trastuzumab
Preferred regimens for HER2 overexpression-negative adenocarcinoma include:
- Fluoropyrimidine (5-FU or Capecitabine) and Cisplatin
- Fluoropyrimidine (5-FU or Capecitabine) and Oxaliplatin
- Fluoropyrimidine (5-FU or Capecitabine) + Oxaliplatin + Nivolumab for tumors with PD-L1 expression levels by CPS¹ ≥5
Other recommended regimens include:
- Docetaxel
- Docetaxel and Cisplatin
- Docetaxel, Cisplatin and Fluorouracil (DCF)
  - Has been recommended as alternative treatment option for the treatment of patients with advanced gastric cancer, including EGJ cancers, in patients who have not received prior chemotherapy
  - However, it was associated with increased myelosuppression and infectious complications
- Docetaxel, Carboplatin and Fluorouracil
- Docetaxel, Oxaliplatin and Fluorouracil
- Fluoropyrimidine (Fluorouracil or Capecitabine)
- Fluoropyrimidine (5-FU or Capecitabine) + Cisplatin + Trastuzumab + Pembrolizumab
  - For HER2 overexpression-positive adenocarcinoma
- Fluoropyrimidine (5-FU or Capecitabine) + Oxaliplatin + Trastuzumab + Pembrolizumab
  - For HER2 overexpression-positive adenocarcinoma
- Fluorouracil and Irinotecan (FOLFIRI)
- Paclitaxel
- Paclitaxel and Cisplatin or Carboplatin
Fluoropyrimidine (5-FU or Capecitabine) + Oxaliplatin + Nivolumab may be useful in HER2 overexpression-negative adenocarcinoma with PD-L1 expression levels by combined positive score (CPS)¹ <5

Second-line or Subsequent Therapy

Choice of agents depends on previous therapy and performance status
Preferred regimens include:
- Docetaxel
- Fam-trastuzumab deruxtecan-nxki
  - For patients with HER2 overexpression-positive adenocarcinoma and received prior Trastuzumab-based therapy
- FOLFIRI
  - For patients who did not previously receive FOLFIRI
- Irinotecan
- Paclitaxel
- Ramucirumab and Paclitaxel
- Trifluridine and Tipiracil
  - Indicated as third-line or subsequent therapy for select patients with low-volume gastric cancer without or minimal symptoms and with the ability to swallow pills
Other recommended regimens include:
- Docetaxel and Irinotecan
- FOLFIRI + Ramucirumab
- Irinotecan and Cisplatin
- Irinotecan and Ramucirumab
- Ramucirumab
Agents useful in certain circumstances include:
- Dostarlimab-gxly is indicated for MSI-high (MSI-H) or MMR-deficient (dMMR) tumors
- Entrectinib or Larotrectinib is used for NTRK gene fusion-positive tumors
- Pembrolizumab is indicated for MSI-H or dMMR tumors or for TMB high (≥10 mutations/megabase) tumors
In patients of adequate performance status, second-line chemotherapy is associated with proven improvements in overall survival and quality of life compared with best supportive care

Targeted Therapies

HER2 testing is recommended for all patients with inoperable, locally advanced, recurrent and metastatic disease at the time of diagnosis
In HER2-positive gastric cancer, addition of Trastuzumab to a Cisplatin-Fluoropyrimidine doublet showed clinically and statistically significant improvements in response rate, progression-free survival and overall survival
- Trastuzumab in combination with Cisplatin and fluoropyrimidine (first-line) or with other chemotherapy agents (eg Capecitabine or 5-fluorouracil and Oxaliplatin) is the standard care regimen
- Trastuzumab was limited only in patients with an IHC score of 3+ or 2+ and FISH positive
- Trastuzumab is not recommended to be continued in second-line therapy
Pembrolizumab is a PD-1 antibody
- Other second-line or subsequent therapy for MSI-H or dMMR tumors or for TMB high (≥10 mutations/megabase) tumors
- May be added to first-line fluoropyrimidine, platinum and Trastuzumab in the treatment of HER2 overexpression-positive adenocarcinoma
Dostarlimab-gxly is a PD-1 antibody
- Indicated for patients with progressive MSI-H or dMMR gastric cancer on or following prior therapy which did not include a checkpoint inhibitor such as PD-1i, PDL-1i, or CTLA4i, and without alternative therapy options
Entrectinib or Larotrectinib is recommended as second-line or subsequent therapy for NTRK gene fusion-positive tumors
Fam-trastuzumab deruxtecan-nxki is an antibody-conjugate composed of Trastuzumab and a cytotoxic topoisomerase I inhibitor which is connected by a cleavable tetrapeptide-based linker
- Preferred second-line or subsequent therapy for patients with HER2 overexpression-positive adenocarcinoma and received prior Trastuzumab-based therapy
Nivolumab is a monoclonal PD-1 antibody
- In combination with fluoropyrimidine- and platinum-based chemotherapy is approved as first-line therapy for patients with HER2-negative advanced or metastatic gastric cancer with PD-L1 expression levels by CPS¹ of ≥5 and may be useful in tumors with a CPS¹ <5
  - Addition of Nivolumab to chemotherapy resulted in significant improvements in overall survival and progression-free survival in patients with a PD-L1 CPS¹ of ≥5
Targeting vascular endothelial growth factor receptors (VEGFR) with the anti-VEGFR-2 monoclonal antibody Ramucirumab showed promising results in patients with advanced gastric or EGJ adenocarcinoma positive for disease progression despite treatment with platinum-/fluoropyrimidine-based doublet/triplet chemotherapy
- Ramucirumab may be given alone or in combination with Paclitaxel

Palliative/Best Supportive Care

Recommended for all patients with unresectable locally advanced, recurrent or metastatic gastric cancer
Goal is to prevent, reduce and relieve suffering and improve the quality of life for patients and their families

Interventional Radiotherapy

Angiographic embolization may be considered in patients with acute bleeding not relieved by endoscopy

Radiotherapy

Hypofractionated radiotherapy is an effective and well-tolerated treatment modality which may palliate bleeding, obstructive symptoms or pain in patients with symptomatic locally advanced or recurrent disease
External beam radiotherapy may be considered for patients with malignant obstruction causing pain, and acute or chronic gastrointestinal bleeding

Surgery

Surgeries that will aid the patients with unresectable gastric cancer control the cancer or prevent or relieve symptoms or complications
Although resection of the primary tumor is not generally recommended in the palliative setting, a small number of advanced disease patients may be deemed to be operable following a good response in systemic therapy
Gastric resections should be reserved for palliation of symptoms such as obstruction or uncontrollable bleeding in patients with incurable disease
- Gastrojejunostomy or gastrectomy may be done to alleviate or bypass obstruction
  - Gastrojejunostomy is preferred for gastric outlet obstruction over endoluminal stenting for patients fit for surgery and with a more prolonged prognosis
- Lymph node dissection is not required

Subtotal gastrectomy can help in problems of bleeding, pain or blockage in the stomach
Limited gastric resection, even with positive margins, is acceptable for unresectable tumors for symptomatic palliation of bleeding
- Presence of peritoneal involvement, distant metastases, or locally advanced disease (eg invasion or encasement of major blood vessels) are contraindications for resection

Routine or prophylactic splenectomy should be avoided if possible
Gastric bypass (gastrojejunostomy) can treat or prevent large tumors that block food from leaving the stomach
- For selected patients who will be receiving postoperative chemoradiation, placement of a venting gastrostomy or jejunostomy feeding tube may be considered

Endoscopic tumor ablation helps to stop bleeding or help relieve blockage without surgery
- For short-term control of bleeding

Stent placement helps keep the opening at the beginning and end of the stomach open and allows food to pass through it
- Endoscopic insertion of self-expanding metal stents (SEMS) has been shown to be effective for the long-term relief of tumor obstruction at the gastric outlet or EGJ
  - Preferred over gastrojejunostomy for patients with luminal obstruction secondary to advanced gastric cancer and with relatively short life expectancy
Venting gastrostomy may be performed to reduce symptoms of obstruction when bypass or alleviation is not possible
Feeding tube placement is done to help in the liquid nutrition that can be put directly into the tube

¹Combined positive score (CPS) is the number of PD-L1 staining cells (eg lymphocytes, macrophages, tumor cells) divided by the total number of viable tumor cells evaluated, multiplied by 100

GP symposium 2019: Updates on the Use of Probiotics in Clinical Practice

Dr. Gwee Kok Ann, Dr. Warren Lee, Dr. Mark Tang, Dr. Lim Sanghyun, 24 Apr 2019

Modulation of gut microbiota with probiotics has been studied in a wide range of clinical settings, in the hope of achieving health benefits in the host. Under the auspices of the Asian GI Faculty, four experts discussed the role of probiotics in clinical practice at the recent IMPACT (Improving Medical Practice through Advancement in Clinical Treatment) GP symposium in Singapore sponsored by DCH Auriga.

Long COVID: What we have learned so far

Prof. Ghassan Dbaibo, 27 Apr 2023

The WHO defines long COVID as a condition that occurs 3 months from COVID-19 onset, whose symptoms last ≥2 months and cannot be attributed to an alternative diagnosis. In an interview with MIMS Doctor, Professor Ghassan Dbaibo of the Center for Infectious Diseases, American University of Beirut, Beirut, Lebanon, describes the evolving attitudes towards long COVID among healthcare professionals (HCPs), some unexpected predisposing factors, potential biological mechanisms behind prolonged symptom duration and shares data on vaccination’s protective effects against long COVID.

Updates in the Management of Gastric Cancer

Prof Yasuhiro Kodera, Prof Winnie Yeo, 23 Jul 2019

Globally, gastric cancer is the third leading cause of cancer death.¹ Its primary treatment is gastrectomy with adjuvant chemotherapy or chemoradiotherapy to improve survival. Although neoadjuvant chemotherapy or adjuvant chemoradiation is preferred in Western countries, postoperative adjuvant chemotherapy is still the mainstream therapeutic strategy in Asia.² At a recent symposium in Hong Kong, experts discussed updates in the treatment and management of gastric cancer, with a focus on the use of S-1 (TS-ONE^®; Taiho Pharma Singapore), a combination of tegafur, gimeracil, and oteracil potassium.