Influence of Taxanes on Treatment Sequence in Gastric Cancer

Sylvie Lorenzen1, Michael Stahl2, Ralf-Dieter Hofheinz3

  • 1Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie, Klinikum rechts der Isar, Munich, Germany, sylvielorenzen@gmx.de.

Abstract

Insights

Standard first-line gastric cancer treatment involves platinum-fluoropyrimidine chemotherapy. While taxanes are not generally recommended first-line due to toxicity and lack of survival benefit, they may be considered for high tumor burden. Sequential therapy is crucial in advanced disease.

Area of Science:

  • Medical Oncology
  • Gastrointestinal Oncology
  • Clinical Trials

Background:

  • Gastric and esophagogastric junction (EGJ) adenocarcinoma presents a poor prognosis.
  • Advances in other solid tumors contrast with negative outcomes in numerous gastric cancer phase III studies.
  • Trastuzumab (HER2-positive) and ramucirumab (anti-angiogenic) represent successful targeted therapies.

Purpose of the Study:

  • To provide an expert consensus on sequential systemic treatment for advanced gastric and EGJ cancer.
  • To evaluate scientific and clinical evidence from randomized controlled trials.

Main Methods:

  • Expert consensus discussion.
  • Review of randomized controlled phase II and phase III clinical trial data.

Main Results:

  • First-line taxane combinations with platinum-fluoropyrimidine are generally not recommended due to toxicity and lack of survival benefit.
  • Taxanes may be considered in first-line for patients with high tumor burden requiring remission.
  • Sequential therapy is increasingly important in metastatic gastric and EGJ cancer based on positive second- and third-line studies.

Conclusions:

  • Standard first-line therapy for gastric cancer is a platinum-fluoropyrimidine chemotherapy doublet.
  • Ramucirumab plus paclitaxel is the standard of care after first-line platinum-based therapy failure.
  • Evidence for this combination after prior taxane therapy is currently unavailable.

Related Concept Videos

Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.6K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
507
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists01:27

Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists

5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
561
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.6K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.8K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
3.6K