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1.
The development of anticancer drugs has conventionally focused on intravenous rather than oral regimens. Recently, interest
in oral administration of chemotherapy has been stimulated by the discovery of oral fluoropyrimidines, which appear to possess
at least an equivalent efficacy and the potential to reduce toxicity compared with intravenous therapies. Using rational drug
design, several oral fluoropyrimidines have been developed, including capecitabine, UFT (tegafur and uracil), eniluracil plus
oral 5-fluorouracil (5-FU), and S-1. In addition to the oral fluoropyrimidines, other novel agents available for potential
oral administration include irinotecan and temozolomide. 相似文献
2.
Novel cytotoxic drugs: old challenges, new solutions 总被引:1,自引:0,他引:1
The discovery of cytotoxic agents was revolutionary for anticancer therapy in the last century, improving survival rates and the quality of life of patients with different types of tumours. However, the development of agents that combine efficacy, safety and convenience remains a great challenge, due to the narrow therapeutic index of some drugs, the fact that they may damage not only cancer cells, but also normal and healthy tissue and the occurrence of resistance, limiting anticancer efficacy. Novel cytotoxic agents have brought certain advantages over the conventional ones, such as shorter administration time, mechanisms to overcome drug resistance and lower incidence of adverse events. In this review we highlight the development of promising novel cytotoxic drugs that will hopefully offer not only gains in efficacy, but also in safety, tolerability and convenience in the treatment of patients with cancer. 相似文献
3.
Saikawa Y Kiyota T Nakamura R Wada N Yoshida M Kubota T Kumai K Shigematsu N Kubo A Kitajima M 《Gan to kagaku ryoho. Cancer & chemotherapy》2006,33(Z1):99-105
A recent development of novel anticancer agents like S-1, CPT-11 or taxanes has improved a therapeutic outcome for advanced gastric cancer, while conventional anticancer agents showed less anticancer effect against gastric cancer. The present main drug in Japan is S-1, which is easily used for outpatient with a high efficacy rate and low toxicity, also shows better effect in combination with other anticancer drugs than S-1 alone. In the present article, we demonstrated significant meaning of additional radiation therapy with anticancer drugs like S-1. With novel anticancer drugs like S-1, we will expose a clinical advantage and appropriateness for chemo-radiation therapy against gastric cancer discussed in the present references according to chemo-radiation therapy. Although chemo-radiation therapy has been recognized as one of the standard therapies for gastric cancer in Western countries, radiation therapy was selected in Japan for palliation therapy of recurrent disease or a terminal cancer to improve patients' QOL. On the other hand, we demonstrated in our trial of chemo-radiation therapy with S-1/low-dose CDDP/radiation (TSLDR), which was applied to initial treatment against highly advanced Stage IV gastric cancer and revealed the usefulness of the regimen in anticancer effect and toxicity. In addition, chemo-radiation therapy including novel anticancer agents like S-1 will be discussed based on various kinds of view points, expecting a better clinical outcome of multimodal therapies against advanced gastric cancer. 相似文献
4.
Traditionally, anticancer therapy has been dominated by intravenous drug therapy. However, oral agents provide an attractive approach to chemotherapy and use of oral treatments is increasing. We discuss the benefits and challenges of oral chemotherapy from the perspectives of patients, healthcare providers and healthcare funders. Important issues include patient preference, efficacy, compliance, bioavailability, reimbursement, use in special patient populations, financial and staff time savings and flexibility of dosing. We review data for traditional oral agents (e.g. cyclophosphamide, methotrexate), newer oral chemotherapies (e.g. capecitabine), oral formulations of traditionally intravenous agents (e.g. vinorelbine, idarubicin) and new biologic agents under evaluation in breast cancer (e.g. tyrosine kinase inhibitors). Lastly, we review studies of all-oral combination regimens. The wealth of data available and the increasing use of oral agents in breast cancer suggest that many of the concerns and perceptions about oral therapy, including efficacy and bioavailability, have been overcome, and that oral therapy will play a major role in breast cancer management in the future in both the metastatic and adjuvant settings. 相似文献
5.
We had 3 patients with recurrent/advanced breast cancer in whom a notable reduction in the size of the targeted tumors was seen following administration of S-1 (TS-1), a new oral pyrimidine fluoride anticancer drug.All of the patients had received taxane and/or anthracycline anticancer drugs as prior therapy; however, they were judged to be non-responsive to the drugs. The size of the targeted tumor decreased to 55.7% after 3 courses of the therapy in Patient 1. The tumor disappeared at completion of the third course in Patient 2, although the therapy was temporarily suspended during the second course due to adverse drug reactions, and the therapy was then resumed after 2-week drug withdrawal. Patient 3 was able to undergo long-term therapy, consisting of 8 courses for 11 months, and the size of the tumor reduced to 58.1%. No serious adverse drug reactions to S-1 occurred in our 3 patients. It is thought that less toxicity enabled Patient 3 to undergo long-term therapy. We consider S-1 to be a useful anticancer drug for treatment of taxane and/or anthracycline resistant recurrent breast cancer. 相似文献
6.
Cassidy J 《Clinical colorectal cancer》2005,5(Z1):S47-S50
One of the most widely used cytotoxic agents is 5-fluorouracil. The use of infusional regimens has become commonplace and with this has come a realization of the limitations of this mode of administration. A number of oral fluoropyrimidines have been developed. Of these, capecitabine is the most established, with registrations in most countries for breast and colorectal cancer. The trials with this agent have mainly attempted to show equivalence with a "standard" intravenous comparator. In most cases, this endpoint has been met or exceeded. In addition, the trials have demonstrated reduced toxicity (except for hand-foot syndrome), and aspects of patient acceptability and cost-effectiveness have been integrated into these studies. Patients seem to prefer oral therapy but not at the expense of anticancer activity. However, the absence of intravenous access devices and complications associated with their use is a major bonus for oral therapy. The drawbacks are somewhat less obvious. Some patients are concerned that oral therapy is in some way inferior (ie, soft option) to intravenous chemotherapy. Compliance with oral therapy is always questionable. Although very few trials in which compliance has been formally assessed have been performed, the issue of overcompliance has not been addressed; in other words, there may be a problem of patients continuing to take the medication even in the face of toxicity and advice to stop treatment. Oral chemotherapy requires just as much care as intravenous chemotherapy and probably requires more attention to patient education and involvement in care decisions. 相似文献
7.
Cassata A Procoplo G Alù M Ferrari L Ferrario E Beretta E Longarini R Busto G De Candis D Bajetta E 《Tumori》2001,87(6):364-371
Fluoropyrimidines remain the most important drugs in the treatment of breast and colorectal carcinoma, but response rates and survival time have been disappointing. Optimal administration is by continuous intravenous infusion, which makes it cumbersome to use and compromises patient independence. Recently, a number of new agents, including fluorouracil prodrugs and selective dihydropyrimidine dehydrogenase inhibitors, have been studied, with promising results. Capecitabine is the first in a new class of fluoropyrimidines. It is an oral, tumor-activated anticancer drug whose activity mimics that of continuously infused 5-fluorouracil. Capecitabine circumvents dihydropyrimidine dehydrogenase catabolism and appears to be at least as active against metastatic colorectal and breast cancer as conventionally administered intravenous 5-fluorouracil, with significantly less toxicity, an improved quality of life, and lesser cost. Capecitabine may ultimately provide enhanced antitumor activity to fluorouracil-containing regimes for advanced colorectal and breast cancer. 相似文献
8.
Nonsteroidal anti-inflammatory drugs in colorectal cancer: from prevention to therapy 总被引:11,自引:0,他引:11
In this review, we discuss the available experimental evidences supporting the chemopreventive efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer and the biological basis for their possible role as anticancer agents. Although the comprehension of the mechanisms underlying the effects of these drugs on colon cancer cells is incomplete, research efforts in identifying the biochemical pathway by which NSAIDs exert their chemopreventive effect have provided a rationale for the potential use of NSAIDs alone or in combination with conventional and experimental anticancer agents in the treatment of colorectal cancer. In this paper, we review three main issues: (i) the role of COX-2 in colon cancer; (ii) the common death pathways between NSAIDs and anticancer drugs; and (iii) the biological basis for the combination therapy with COX-2 selective inhibitors and new selective inhibitors of growth factor signal transduction pathways. 相似文献
9.
Murata S Kominsky SL Vali M Zhang Z Garrett-Mayer E Korz D Huso D Baker SD Barber J Jaffee E Reilly RT Sukumar S 《Cancer research》2006,66(2):638-645
In cancer patients and in those at high risk, systemic exposure to agents for therapy or prevention is accompanied by undesirable side effects. We hypothesized that it is possible to prevent and treat breast cancer by introducing anticancer agents into the mammary ductal network. Here, we show the efficacy of intraductally administered anticancer agents 4-hydroxytamoxifen and pegylated liposomal doxorubicin (PLD) in the prevention and treatment of breast cancer using the rat N-methyl-N'-nitrosourea-induced and spontaneous HER-2/neu transgenic mouse (neu-N) models of breast cancer. Intraductal administration of PLD to neu-N mice caused regression of established tumors and prevented tumor development more effectively than i.v. injection (P < 0.0001). Intraductal administration resulted in lower circulating levels of PLD compared with i.v. administration, with no evidence of systemic toxicity or long-term histopathologic changes in the mammary gland. Compared with systemic administration, intraductal injection provides direct access to breast lesions with higher local and lower systemic drug exposure. These studies suggest that this approach has potential for application to prevention and neoadjuvant therapy of early breast cancer. 相似文献
10.
Concurrent with the development of new antitumor drugs, there is intensive research to develop strategies and systems to optimize the efficacy of well-known anticancer agents. The main research lines are: (a) reduction in toxicity, (b) improvement of administration and (c) overcoming drug resistance. Drug targeting systems allow us to act on these three points. The best way to increase efficacy and reduce toxicity of an anticancer agent is targeting the drug at the level of the tumor masses and maintaining its concentration there for enough time to optimize its therapeutic action. Numerous strategies have been developed to achieve this second order targeting, based on the use of polymeric-drug conjugates, polymeric micelles, liposomes and albumin conjugates and nanoparticles, whose main features of toxicity, efficacy and administration are discussed in this review. 相似文献
11.
12.
5-Fluorouracil (5-FU) has been utilized as part of standard chemotherapy for treatment of early-stage and metastatic colorectal cancer for more than 4 decades. The oral fluoropyrimidines have been studied extensively as an alternative to intravenous 5-FU. The goal of such an approach is to simplify drug administration and to improve the toxicity profile while maintaining efficacy that is at least equivalent to intravenous therapy. The goal of this article is to review the features of the main oral 5-FU prodrugs, which include capecitabine, uracil and tegafur (UFT)/leucovorin, S-1, and BOF-A2 and to describe their potential efficacy in treating colorectal cancer. 相似文献
13.
Xiang Kang Hai-Hua Xiao Hai-Qin Song Xia-Bin Jing Le-San Yan Ruo-Gu Qi 《癌症生物学与医学(英文版)》2015,12(4):362-374
Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost all the platinum drugs developed. To conquer these problems, new strategies should be adopted for platinum drug based chemotherapy. Modern nanotechnology has been widely employed in the delivery of various therapeutics and diagnostic. It provides the possibility of targeted delivery of a certain anticancer drug to the tumor site, which could minimize toxicity and optimize the drug efficacy. Here, in this review, we focused on the recent progress in polymer based drug delivery systems for platinum-based combination therapy.KEYWORDS : Cancer, drug delivery, combination therapy, platinum 相似文献
14.
Joseph J. DeGeorge Chang-Ho Ahn Paul A. Andrews Margaret E. Brower Diana W. Giorgio M. Anwar Goheer Doo Y. Lee-Ham W. David McGuinn Wendelyn Schmidt C. Joseph Sun Satish C. Tripathi 《Cancer chemotherapy and pharmacology》1997,41(3):173-185
The entry of new anticancer treatments into phase I clinical trials is ordinarily based on relatively modest preclinical
data. This report defines the battery of preclinical tests important for assessing safety under an Investigational New Drug
application (IND) and outlines a basis for extrapolating starting doses of investigational anticancer drugs in phase I clinical
trials from animal toxicity studies. Types of preclinical studies for the support of marketing of a new anticancer drug are
also discussed. This report addresses differences and similarities in the preclinical development of cytotoxic drugs (including
photosensitizers and targeted delivery products), drugs used chronically (chemopreventive drugs, hormonal drugs, immunomodulators),
and drugs intended to enhance the efficacy (MDR-reversing agents and radiation/chemotherapy sensitizers) or diminish the toxicity
of currently used anticancer therapies. Factors to consider in the design of preclinical studies of combination therapies,
alternative therapies, and adjuvant therapies in the treatment of cancer, and to support changes in clinical formulations
or route of administration, are also discussed.
Received: 19 December 1996 / Accepted: 2 June 1997 相似文献
15.
F. Lokiec 《Oncologie》2007,9(3):HS37-HS40
Toxic side effects are indissociable from anticancer drugs. Today, we face a newphenomenon: oral administration. Toxic side effects, which are relative lymild after intravenous administration and include grades 1–2 nausea and vomiting, have become a major problem with the increase in oral drug administration. Most of theoral forms are new formulations of long-used anticancer agents. Many of them are well known to be emetic. The popularity of these oral forms is well justified because they allow patients to receive treatment at home and avoid excessive hospital stays, which is especially relevant to older patients. But what is recommended in the case of vomiting? Should patients take yet another capsule or tablet? The small molecules used in targeted cancer therapies have the advantage of causing only mild, if any, side effects of this kind. They pose fewer problems even if other side effects, such as dermatological problems, remain constant. 相似文献
16.
Nucleoside analogs are important components of treatment regimens for various malignancies. Nucleoside-specific membrane transporters
mediate plasma membrane permeation of physiologic nucleosides and most nucleoside analogs, for which the initial event is
cellular conversion of nucleosides to active agents. Understanding of the roles of nucleoside transporters in nucleoside drug
toxicity and resistance will provide opportunities for potentiating anticancer efficacy and avoiding resistance. Because transportability
is a possible determinant of toxicity and resistance of many nucleoside analogs, nucleoside transporter abundance might be
a prognostic marker to assess drug resistance. Elucidation of the structural determinants of nucleoside analogs for interaction
with transporter proteins as well as the structural features of transporter proteins required for permeant interaction and
translocation will lead to “transportability guidelines” for the rational design and therapeutic application of nucleoside
analogs as anticancer drugs. It should eventually be possible to develop clinical assays that predict sensitivity and/or resistance
to nucleoside anti-cancer drugs and thus to identify those patient populations that will most likely benefit from optimal
nucleoside analog treatments. This review discusses recent results from structure/function studies of human nucleoside transporters,
the role of nucleoside transport processes in the cytotoxicity and resistance of several anticancer nucleoside analogs and
strategies to improve the nucleoside transporter-related anticancer effects of nucleoside analogs. 相似文献
17.
Identification of the role of biological pathways in metastatic renal cell carcinoma (mRCC) has led to the development of targeted agents for its treatment, in particular those that inhibit the vascular endothelial growth factor pathway, and inhibitors of mammalian target of rapamycin (mTOR). mTOR is central to signalling pathways that regulate cellular growth, proliferation and survival, and this paper focuses on the two currently licensed mTOR inhibitors, temsirolimus and everolimus. These agents are administered via different routes (intravenously and orally, respectively), and this has an impact on their pharmacokinetics; intravenous temsirolimus is not affected by variable absorption in the gastrointestinal tract or by food intake, unlike the orally administered mTOR inhibitor everolimus. Temsirolimus is administered weekly, whereas everolimus is currently approved for daily dosing. In general, intravenous administration is likely to ensure better control of plasma drug concentrations, greater treatment adherence, and more regular monitoring of toxicity and therapeutic response, although it can be uncomfortable and inconvenient for patients. Oral administration is preferred by patients for its convenience, but can be associated with suboptimal adherence to treatment, and poor and variable bioavailability. Temsirolimus and everolimus have both been associated with improved outcomes in patients with mRCC but, as reviewed in this paper, the pharmacokinetic characteristics of these agents differ in many respects. 相似文献
18.
Oral chemotherapy presents a number of theoretical advantages in older cancer patients, including convenience of administration and dosage flexibility. Of the oral fluorinated pyrimidines, capecitabine is the most promising, because it minimizes the exposure of normal tissue to the active drug and substantially reduces the risk of mucositis, that is particularly common and severe in the aged. Despite promising initial results, oral etoposide does not offer any special advantage over the intravenous formulation for older patients, while oral temozolomide may have a role in the palliation of malignant melanoma and primary and secondary brain tumors. Of the experimental agents, oral platinum (satraplatin) and oral taxane formulations appear to be the most promising for minimization of the toxicity of the corresponding intravenous drug. Of special interest are tumor-specific agents, including inhibitors of tyrosine phosphokinase (e.g. imatinib mesylate) and angiogenesis. In conclusion, oral chemotherapy of cancer appears to be a very promising option for older patients. 相似文献
19.
Jaime Feliu Batlle Enrique Espinosa Arranz Javier de Castro Carpeño Enrique Casado Sáez Pilar Zamora Auñón Andrés Redondo Sánchez Manuel González Barón 《Clinical & translational oncology》2004,6(6):335-340
Although oral chemotherapeutic agents have been available for the last 50 years, some reservations about their efficacy and the limited interest of pharmaceutical companies have hampered their widespread use. This situation will probably change in the near future as several new oral anticancer agents have been approved and there are more in development. Convenience and easiness of administration make of oral chemotherapy an attractive option. It avoids the complications and costs derived from intravenous chemotherapy, while maintaining the patients' quality of life. It also allows the replacement of drugs that require protracted administration periods. On the other hand, variable bioavailability and non-compliance appear as the main problems: the former depends on the pharmacological characteristics of the compound, whereas the latter involves time to train the patients and their families and to perform a close follow-up. With an increasing number of oral agents emerging (both traditional cytotoxic and novel, targeted agents), we can expect that oral chemotherapy will become part of daily practice rather than the exception. 相似文献
20.