Introduction

The fixed combination of trifluridine / tipiracil (trade name: Lonsurf) has been approved in Germany since April 2016 for the treatment of metastatic colorectal cancer. The drug is a treatment option for adults with metastatic colorectal cancer that progresses despite treatment or who can't have certain treatments.

Bowel cancer almost always develops from a particular kind of bowel polyp (adenoma). These are non-cancerous (benign) growths in the mucous membrane of the bowel. Most adenomas remain small and are not dangerous. Only few of them change and become cancerous (malignant). Although the small intestine is quite a lot longer than the large intestine, bowel cancer almost always develops in the large intestine (colon) or the rectum. These types of cancer are also called colorectal carcinoma.

Bowel cancer often doesn’t cause any symptoms at first, so it may remain unnoticed for a while. In advanced metastatic bowel cancer, the tumor has spread to other parts of the body and complete recovery is generally no longer possible.

The new fixed drug combination trifluridine / tipiracil aims to prevent cell division and growth in order to slow tumor growth and prevent the cancer from progressing.

Application

The drug is available in tablet form in two different doses: 15 mg of trifluridine / 6 mg of tipiracil, and 20 mg of trifluridine / 8 mg of tipiracil. The dose is determined by the doctor based on the patient's body surface area. A typical dose would be 35 mg of trifluridine per square meter of body surface area.

The drug is used in treatment cycles of 28 days each: During the first five days, it is taken twice per day. This is followed by a two-day break from use of the drug, which is then taken twice a day again for five days. After a total of 28 days the next treatment cycle begins.

Treatment is stopped if the cancer progresses or if serious side effects arise.

Other treatments

Best supportive care (BSC) is the standard treatment for patients with metastatic colorectal cancer for whom previous chemotherapy using the drugs fluoropyrimidine, oxaliplatin or irinotecan, as well as VEGF- or EGFR-targeted treatments, were not effective or not possible. Supportive care should be tailored to the patient's individual needs, relieve symptoms such as pain, and improve quality of life.

Assessment

In 2016, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into which advantages and disadvantages trifluridine / tipiracil has for adults with metastatic colorectal cancer compared with the standard treatment BSC.

The manufacturer provided one study involving a total of 800 people. 534 patients were given the new fixed drug combination trifluridine / tipiracil and BSC, while the remaining 266 people received BSC and a placebo (fake drug). The study only included patients for whom physical activity was either slightly affected or not at all affected by their medical condition. The manufacturer did not provide any studies on people who were no longer able to work or who required nursing care due to the cancer.

What are the advantages of trifluridine / tipiracil?

  • Life expectancy: The study provides weak evidence that the fixed combination of trifluridine / tipiracil has an advantage over the standard treatment. Half of the people who received the fixed combination and best supportive care (BSC) had passed away within about seven months. Of those receiving best supportive care (BSC) only, half had already died within about five and a half months.

What are the disadvantages of trifluridine / tipiracil?

  • Severe side effects: The study showed weak evidence of a disadvantage for additional trifluridine / tipiracil treatment: Half of the people in this group developed serious side effects such as anemia or agranulocytosis accompanied by fever within the first two months. It took nearly three months before half of the people receiving best supportive care had developed serious side effects.

What remains unanswered?

The manufacturer did not provide any suitable data on the following:

  • Symptoms of the disease
  • Health-related quality of life
  • Treatment stopped due to side effects

More information

This information summarizes the main results of a review produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The review was commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of the review and the hearings received, the G-BA passed a resolution on the added benefit of trifluridine / tipiracil (Lonsurf).