title: [Development of molecular targeting drugs for the treatment of cancer-therapeutic potential and issues to be addressed in global development].
abstract: A survey of cancer treatment in a sample of hospitals > 100 beds conducted in 1998 compared with experience in the US showed that good progress has been achieved in Japan in the screening and early treatment of gastric cancer, and that the prognosis for breast cancer is better than in the West. Although in the past, the cytotoxic therapies available to physicians in Japan vs the West have been different, recent acceleration of regulatory review will result in a convergence of treatment paradigms and some improvement in acute response in many tumour types. However, world wide there is a need for new improved therapies in all cancers evaluated. Particular needs are in the management of NSCLC, advanced disease and cancers which form micrometastases. The eventual hope is that cancer can be turned from a lethal disease into a chronic disease where patients maintain a good QOL. Apart from anti hormonal therapies, the usual approach has been to kill the cancerous cells. However, the new approaches to intervening in the growth and migration of cancerous cells or the host tissue response by molecular targeting offer the promise of achieving a step change in therapy. Although EGF tyrosine Kinase inhibitors such as ZD 1839 have been shown to cause a conventional tumour response in NSCLC, many of these new approaches are unlikely to show a short term response even if they have the capacity to affect tumour development and increase disease free survival. Some compounds will require combination therapy with a conventional cytotoxic or radiotherapy to show their full benefit. For conventional cytotoxics, the usual approach to development has been to select the maximum tolerated dose and then evaluate the efficacy in advanced disease. However, for the new approaches which will not have such severe dose limiting toxicities, it will be necessary to select a surrogate marker of the intended biological effect to select the optimal biological dose (OBD) and dose regimen in phase I/II studies for further evaluation in phase II or III studies which are designed to show the expected patient benefit. The tumour target, the stage of the disease and the possible need for concomitant therapy will also have to be considered according to the mechanism of action of the product.
authors.affiliation: Dept. of Urology, University of Tsukuba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Akaza
authors.forename: K
authors.initials: K
authors.lastname: Aiba
authors.forename: S
authors.initials: S
authors.lastname: Isonishi
authors.forename: O
authors.initials: O
authors.lastname: Ogawa
authors.forename: M
authors.initials: M
authors.lastname: Shibuya
authors.forename: S
authors.initials: S
authors.lastname: Sone
authors.forename: T
authors.initials: T
authors.lastname: Tsuruo
authors.forename: S
authors.initials: S
authors.lastname: Noguchi
authors.forename: S
authors.initials: S
authors.lastname: Hinotsu
authors.forename: S
authors.initials: S
authors.lastname: Kono
authors.forename: O
authors.initials: O
authors.lastname: Mikami
authors.forename: G
authors.initials: G
authors.lastname: Blackledge
authors.forename: B
authors.initials: B
authors.lastname: Vose
authors.forename: D
authors.initials: D
authors.lastname: Stribling
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000556:secondary; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D014481:United States
chemical_list: D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil