Close-Up - Development of Anticancer Drugs

Our Heritage: Taking on the Challenge of Developing Anticancer Drugs to Improve Cancer Treatment Worldwide

  • Taiho's development of anticancer drugs began with the synthesis of Futraful at the Institute of Organic Synthesis in Riga, the capital of Latvia.

Intuition that led to the development of creative new drugs, and the spirit of challenge to persevere through difficulties

In 1969, Taiho Pharmaceutical’s first president, Yukio Kobayashi, visited the former Soviet Union for business discussions on Pantocrin Injection, a drug to ameliorate general malaise for which demand had suddenly started to increase at the time. During the visit, Kobayashi devoted every spare moment to visit pharmaceutical-related sites. At a cancer research center in Moscow, he happened to see an ampule of Futraful injection, a derivative of a novel anticancer drug, 5-fluorouracil (5-FU). Guided by intuition, Kobayashi sensed its great potential and instantly decided to conduct clinical trials in Japan. After returning to Japan, he immediately established an anticancer team in the research center to initiate a research program. After confirming the drug’s efficacy in basic research, the drug was taken into clinical trials. However, satisfying clinical results were not obtained, with investigators presenting negative reports on efficacy at the first investigators’ meeting. There was, however, one report on a patient with metastatic breast cancer which showed efficacy, and this case became a ray of hope. Meanwhile, it was reported that Futraful is effective when given at low concentration with exposure to cancer cells for a long period, and this accelerated the basic research. As a result, it was clarified that Futraful is converted into 5-FU through degradation in the liver and shows activity, and also that long-term exposure to cancer cells exerts a sufficient anticancer effect even at low blood concentration. This shifted the direction to the development of an oral anticancer agent, which had never been generally viable in the world at that time. It was then, April of 1972, when the possibility created by intuition started moving steadily toward becoming a reality.

Redefining cancer treatment by bringing small buds of potential to fruition

  • Futraful injection 400mg Pamphlet
    Futraful injection 400mg Pamphlet

Futraful is an antimetabolite and a prodrug of 5-FU which exerts its pharmacological effect by being gradually metabolized into 5-FU in the body. It attracted a great deal of attention in Japan when first developed. An antimetabolite is a kind of anticancer agent which prevents cell division of cancer cells by encouraging uptake of “fake pieces” into cancer cells. Futraful is a drug which utilizes one of these “fake pieces,” a substance called 5-FU. Taiho Pharmaceutical focused on this characteristic of Futraful to demonstrate its efficacy through long-term contact with cancer cells. In 1974, the product was launched in Japan as an anticancer drug that could be administered orally, which was not common in the global general practice at that time.

Unlike conventional anticancer drugs, Futraful enabled long-term oral administration with minimum side effects, creating a new treatment methodology—adjuvant chemotherapy. Moreover, while I.V.-based treatment with anticancer drugs had routinely been accepted up to that point, the availability of oral administration enabled outpatient therapy.


Launched Futraful injection 400mg and the orally available Futraful capsule 200mg in Japan, which drastically changed cancer treatment

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    The photo shows products at the time of initial launch.

Persisting with every challenge to make the product into a globally recognized anticancer drug

Ten years later, Taiho Pharmaceutical succeeded in further extending the sustainability of 5-FU blood concentration by compounding Futraful with uracil. UFT, launched in 1984, was developed also with a mitigation of side effects. Clinical trials for UFT have been conducted for various cancers, and abundant evidence has been created, mainly for adjuvant chemotherapy. Today, UFT is used as one of the primary choices of anticancer drugs, based on the evidence obtained in these clinical studies. Building on this success with UFT, research was advanced to pursue a new drug with stronger efficacy and fewer side effects. The result was the discovery of gimeracil, which prolongs the blood concentration of 5-FU further than uracil, and oteracil potassium, which reduces side-effect damage to the gastrointestinal tract. These two new compounds were compounded with Futraful as the principal component to create TS-1. TS-1 demonstrated a high response rate of 46.5% in a clinical trial in patients with metastatic gastric cancer and was accordingly given a priority review by the Ministry of Health, Labor and Welfare. The product was approved and launched in 1999. Furthermore, it was confirmed in a comparison study that the combination therapy using UFT and UZEL, an oral reduced folic acid formulation, was as efficacious as 5-fluorouracil/leucovorin (5-FU/LV) injection, the global standard therapy at that time. Then, a Japan-US bridging study was conducted and UZEL tablet was launched in Japan in September 2003.


Launched UFT combination capsule T100 in Japan, which pursued stronger efficacy and longer-lasting effect than Futraful

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    The photo shows products at the time of initial launch.


Launched TS-1 combination capsule T20/T25 in Japan, which realized stronger efficacy and reduced the side effects of 5-FU

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    The photo shows products at the time of initial launch.

Careful nurturing of a drug creates new possibilities

In 2004, data from a clinical trial of UFT in the adjuvant setting in patients with lung cancer who had undergone a curative operation was published in the New England Journal of Medicine (NEJM), a medical journal which is among the most prestigious in the world. Thereafter, articles were published one after another on UFT as adjuvant chemotherapy in cancers such as gastric cancer, colorectal cancer, and breast cancer. Similar to UFT, TS-1 has also shown its efficacy against various cancers and has been introduced in global medical journals including the NEJM. A body of evidence has been built up for TS-1, mainly for gastric cancer, followed by cancers such as colorectal cancer, lung cancer, and pancreatic cancer. TS-1 is described in various guidelines and is contributing to cancer treatment. Even now many medical and research institutions are reporting excellent clinical results for TS-1 in numerous medical journals, broadening its possibilities together with the evolution of cancer treatment.


Launched UZEL tablet 25mg in Japan, aiming to enhance the benefit of UFT. In 2008, launched downsized UZEL tablets in Japan, at approximately half the previous weight, for easier administration

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    The photo shows the half-weight type.


Launched TS-1 combination granule T20/T25 in Japan, a granular preparation in a stick-type package which dissolves quickly, enabling easier administration

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Supporting the present and pioneering the future of cancer treatment

In recent years, Taiho Pharmaceutical has been conducting R&D aimed at comprehensive care in oncology from the patient perspective. Striving to contribute to better quality of life for patients undergoing cancer treatment, the company has launched products such as TS-1 combination granule, which dissolves quickly and enables easier administration for cancer patients with swallowing difficulties, Aloxi, an antiemetic agent which relieves nausea and vomiting associated with chemotherapy, and E-fen, a fentanyl buccal tablet which relieves cancer pain (breakthrough pain). In 2009, the company acquired a research center in Tsukuba that was part of the former Banyu Pharmaceutical Co., Ltd. and consolidated all of its in-house drug discovery functions into this Tsukuba Area. Cutting-edge technology is now being applied to aggressively develop new types of anticancer drugs. Taiho Pharmaceutical in-licensed the anticancer drug Abraxane, which has been approved in over 65 countries*1 worldwide. The company pursued the development of the drug in Japan, where it was launched in 2010 as a breast cancer treatment. Later, additional indications were approved for gastric cancer, non-small cell lung cancer, and unresectable pancreatic cancer.


*1: As of January 2017. Taiho Pharmaceutical holds the development and marketing rights in Japan

Launched Aloxi I.V. injection 0.75mg in Japan, which controls the nausea and vomiting associated with cancer chemotherapy

  • 2010_image

Launched Abraxane I.V. infusion 100mg in Japan, an anticancer drug that has been approved in more than 65 countries*1

  • 2010_image


Launched TS-1 combination OD tablet T20/T25, an orally disintegrating anticancer agent, in Japan

  • 2013_image
    The photo shows products at the time of initial launch.

Launched E-fen buccal tablet, a cancer pain reliever for breakthrough pain, in Japan


Launched LONSURF combination tablet T15/T20, an oral anticancer drug for unresectable advanced or recurrent colorectal cancer, in Japan

  • 2014_image


Launched Yondelis I.V. infusion 0.25mg/1mg, an anticancer agent for the treatment of soft tissue sarcoma, in Japan

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Delivering novel drugs originating in Japan to patients around the world

TS-1 has become the standard treatment for gastric cancer in Japan and is sold in 10 other countries and regions*2 in Asia. After receiving approval in Europe in 2011, TS-1 is now marketed in 19 countries*2 in that region. In May 2014, the anticancer agent LONSURF was first launched in Japan for the treatment of unresectable advanced or recurrent colorectal cancer.
In October 2015, LONSURF was then launched in the U.S., becoming the first product for which Taiho obtained U.S. FDA approval. In April 2016, approval for the drug was granted by the European Commission, and sales are being expanded in countries there.*2
In its 40-plus year history of anticancer drug research and development, Taiho Pharmaceutical has established a great body of evidence in cancer chemotherapy, making it one of Japan’s leading companies in this field. Transforming that abundant experience into a dynamic asset, the company seeks to help cancer patients in Japan and around the world.

*2: As of December 2016