Efficacy clinical trials

Treatment Pharmacology and positive attributes Efficacy (clinical trials) Limitations... 

Mystakidou K, Befon S, Kouskouni E, Gerolymatos K, Georgaki S, Tsilika E, Vlahos L. From codeine to transdermal fentanyl for cancer pain control a safety and efficacy clinical trial. Anticancer Res 2001 21(3C) 2225-30. 

Regulatory framework safety, efficacy, clinical trials... 

The preclinical trials are performed in in vitro and animal studies to assess the biological activity of the new compound. In phase 1 of the clinical trials the safety of a new drug is examined and the dosage is determined by administering the compound to about 20 to 100 healthy volunteers. The focus in phase II is directed onto the issues of safety, evaluation of efficacy, and investigation of side effects in 100 to 300 patient volimteers. More than 1000 patient volunteers are treated with the new drug in phase 111 to prove its efficacy and safety over long-term use. 

Human growth hormone, used as a human pharmaceutical, is approved for only one indication in the United States, treatment of growth failure owing to hGH deficiency, a condition known as pituitary dwarfism. However, clinical trials are under way to test its efficacy in Turner s syndrome, bums, wound healing, cachexia, osteoporosis, constitutional growth delay, aging, malnutrition, and obesity. 

Clinical trials for r-IEN-y in RA indicated that the dmg is well tolerated (52). Consistent improvement in tender and swollen joint scores was observed, but a large number of patients were needed in the trial to show statistical significance for r-IEN-y treatment. In certain individuals, responses were remarkable. An additive effect between r-IEN-y and penicillamine was detected. Efficacy was lower when r-IEN-y was combined with gold therapy. Research is continuing. 

Influenza. Although current influenza vaccine (subunit spHt vaccine) has been in use yearly for the elderly, it is not recommended for the general population or infants. Improvements to increase or prolong the immunogenicity, reduce the side-effects (due to egg production procedure), and provide mass protection are stiU being pursued. One approach is to use a five, attenuated vims though cold adaptation. A vaccine has been used in Russia and demonstrated to be safe and efficacious for infants (82). Clinical trials for a similar vaccine are being carried out in the United States (83). 

One of the early vaccine candidates was directed against sporo2oites, the form of the parasites that is first injected into the host by a mosquito. With recent development of recombinant techniques, several circumsporo2oite proteins or its related peptides were proposed as the vaccine candidates. Clinical trials have been carried out. The vaccines were immunogenic, but did not provide sufficient protective efficacy (90,91). 

Adjuvants are substances which can modify the immune response of an antigen (139,140). With better understanding of the functions of different arms of the immune system, it is possible to explore the effects of an adjuvant, such that the protective efficacy of a vaccine can be improved. At present, aluminum salt is the only adjuvant approved for use in human vaccines. New adjuvants such as QS-21, 3D-MPL, MF-59, and other liposome preparations are being evaluated. Several of these adjuvants have been in clinical trial, but none have been approved for human use. IL-12 has been proposed as an adjuvant which can specifically promote T-helper 1 ceU response, and can be a very promising adjuvant for future vaccine development. 

L-Asparaginase is used for the treatment of appropriate lymphoproliferative disorders in two clinical trials, L-asparaginase was used in combination with chemotherapy for the treatment of refractory acute nonlymphocytic leukemia in children (24) and adults (25). A moderate efficacy, attributable to the enzyme, was demonstrated in both trials. 

For the past few years, however, there has been a hiatus in the pace of discovery of novel medicinal agents. It has been postulated by some that the field has now slowed down due to the limitations of the almost strictly empirical approach that has been applied to date to drug development. It is possible, too, that the higher standards of efficacy and safety that a new drug must meet today, combined with the enormously increased costs of clinical trials, have acted to keep all but the most promising new drugs off the market. 

Drugs can only be effective if enough is present at the target site and they can be harmful if too much is present so as to produce toxic side effects. Any attempt to draw conclusions about the clinical efficacy of a drug in a clinical trial without knowledge of the concentration at the target site is premature. The science of pharmacokinetics basically... 

Clinical trials showed therapeutic efficacy in a broad spectrum of tumors these include SCLC, testicular tumors, sarcomas, breast cancer, renal cell cancer, pancreatic tumors and lymphomas. Ifosfamide is less myelosuppressive than cyclophosphamide but is more toxic to the bladder. Therefore it is recommended that ifosfamide is coadministered with the thiol compound mesna to avoid hemorrhagic cystitis and to reduce the risk of developing bladder cancer. Other side effects include neurotoxicity and myelosuppression. 

The first clinical trials were performed in the 1970 s using a sodium salt derivative with an open E-ting (Fig. 1). However, the clinical efficacy was limited and severe bladder toxicity led to the termination of the clinical trials. The poor efficacy of the camptothecin sodium salt in those clinical trials was probably due to the fact that the open E-ring form of camptothecin (carboxylate derivative) is inactive as a Topi inhibitor. Following the identification of Topi as a target of camptothecin, water-soluble derivatives were produced by the pharmaceutical industry. Two of these water-soluble derivatives have been approved by the FDA for cancer treatment in the early 2000s topotecan and irinotecan. 

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