Derazantinib: an investigational drug for the treatment of cholangiocarcinoma

Drug–drug interactions (DDIs) can cause drug toxicities, reduced pharmacological effects, and adverse drug reactions. Studies aiming to determine the possible DDIs for an investigational drug are part of the drug discovery and development process and include an assessment of the DDIs potential mediated by inhibition or induction of the most important drug-metabolizing cytochrome P450 isoforms. Our study was dedicated to creating a computer model for prediction of the DDIs mediated by the seven most important P450 cytochromes: CYP1A2, CYP2B6, CYP2C19, CYP2C8, CYP2C9, CYP2D6, and CYP3A4. For the creation of structure–activity relationship (SAR) models that predict metabolism-mediated DDIs for pairs of molecules, we applied the Prediction of Activity Spectra for Substances (PASS) software and Pairs of Substances Multilevel Neighborhoods of Atoms (PoSMNA) descriptors calculated based on structural formulas. About 2500 records on DDIs mediated by these cytochromes were used as a training set. Prediction can be carried out both for known drugs and for new, not-yet-synthesized substances. The average accuracy of the prediction of DDIs mediated by various isoforms of cytochrome P450 estimated by leave-one-out cross-validation (LOO CV) procedures was about 0.92. The SAR models created are publicly available as a web resource and provide predictions of DDIs mediated by the most important cytochromes P450.

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Paclitaxel activity in heavily pretreated breast cancer: a National Cancer Institute Treatment Referral Center trial.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.8.2056 ◽

1995 ◽

Vol 13 (8) ◽

pp. 2056-2065 ◽

Cited By ~ 85

Author(s):

J S Abrams ◽

D A Vena ◽

J Baltz ◽

J Adams ◽

M Montello ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Progressive Disease ◽

Overall Response Rate ◽

Metastatic Breast ◽

Investigational Drug ◽

Single Institution ◽

Doxorubicin Treatment ◽

Heavily Pretreated ◽

Pretreated Patients

PURPOSE To provide paclitaxel, an investigational drug at the inception of this study, to women with chemotherapy-refractory metastatic breast cancer and to evaluate response and toxicity in these patients. PATIENTS AND METHODS Two hundred sixty-seven patients with progressive disease (PD) following at least two chemotherapy regimens for metastatic breast cancer and a contraindication to further doxorubicin treatment received paclitaxel either at 175 mg/m2 intravenously (IV) over 24 hours or at 135 mg/m2 if they had prior irradiation to 30% of marrow-bearing bone or a cumulative dose of mitomycin > or = 20 mg/m2. RESULTS In a subgroup of patients (n = 172) with measurable disease, four complete responses (CRs) and 36 partial responses (PRs) occurred, for an overall response rate of 23% (95% confidence interval [CI], 17% to 30%). No differences in response rates were noted according either to the number of prior chemotherapy regimens received or to whether patients were considered refractory to doxorubicin. The dose and schedule used in this trial resulted in febrile neutropenia in 45% of patients and a hospitalization rate of 49%. CONCLUSION Paclitaxel's activity in this multiinstitutional trial in heavily pretreated patients confirms the encouraging results attained in single-institution trials. Although at this dose and schedule paclitaxel may be considered too myelosuppressive for palliative care, supportive measures such as colony-stimulating factors and antibiotics were not used prophylactically. Current research efforts are focusing on whether paclitaxel's activity against breast cancer is dose- and/or schedule-dependent, and on what role it has in patients with less advanced disease.

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Use of failure modes and effects analysis to mitigate potential risks prior to implementation of an intravenous compounding technology

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/zxab179 ◽

2021 ◽

Author(s):

Agnes Ann Feemster ◽

Melissa Augustino ◽

Rosemary Duncan ◽

Anand Khandoobhai ◽

Meghan Rowcliffe

Keyword(s):

Medication Safety ◽

Failure Modes ◽

Risk Mitigation ◽

New Technology ◽

Hazard Index ◽

Mitigation Strategies ◽

Investigational Drug ◽

Workflow Optimization ◽

Proactive Approach ◽

Risk Mitigation Strategies

Abstract Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose The purpose of this study was to identify potential failure points in a new chemotherapy preparation technology and to implement changes that prevent or minimize the consequences of those failures before they occur using the failure modes and effects analysis (FMEA) approach. Methods An FMEA was conducted by a team of medication safety pharmacists, oncology pharmacists and technicians, leadership from informatics, investigational drug, and medication safety services, and representatives from the technology vendor. Failure modes were scored using both Risk Priority Number (RPN) and Risk Hazard Index (RHI) scores. Results The chemotherapy preparation workflow was defined in a 41-step process with 16 failure modes. The RPN and RHI scores were identical for each failure mode because all failure modes were considered detectable. Five failure modes, all attributable to user error, were deemed to pose the highest risk. Mitigation strategies and system changes were identified for 2 failure modes, with subsequent system modifications resulting in reduced risk. Conclusion The FMEA was a useful tool for risk mitigation and workflow optimization prior to implementation of an intravenous compounding technology. The process of conducting this study served as a collaborative and proactive approach to reducing the potential for medication errors upon adoption of new technology into the chemotherapy preparation process.

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Effect of new investigational drug taxol on oncolytic activity and stimulation of human lymphocytes

International Journal of Gynecology & Obstetrics ◽

10.1016/0020-7292(94)90216-x ◽

1994 ◽

Vol 44 (3) ◽

pp. 308-308

Author(s):

L.T. Chuang ◽

E. Lotzova ◽

K.R. Cook ◽

P. Cristoforoni ◽

M. Morris ◽

...

Keyword(s):

Human Lymphocytes ◽

Investigational Drug ◽

Oncolytic Activity ◽

Stimulation Of

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Therapeutic Discourse Among Nurses and Physicians in Controlled Clinical Trials

Nursing Ethics ◽

10.1177/0969733008095388 ◽

2008 ◽

Vol 15 (6) ◽

pp. 803-812 ◽

Cited By ~ 7

Author(s):

Susan L Instone ◽

Mary-Rose Mueller ◽

Tari L Gilbert

Keyword(s):

Informed Consent ◽

Term Treatment ◽

Investigational Drug ◽

Extensive Literature ◽

Drug Trials ◽

Treatment Trial ◽

Controlled Clinical Trials ◽

Professional Characteristics ◽

Nurses And Physicians ◽

Seriously Ill

An ethnographic field study about the informed consent process in investigational drug trials for seriously ill persons with hepatitis C suggests that nurses and physicians referred to these trials as giving treatment, even though they involved placebos. Interview data and informed consent documents contained frequent references to the term `treatment trial' or `treatment'. Although these findings were unexpected and not the original focus of our study, we consider them in the light of an extensive literature on the `therapeutic misconception' that has been described among physicians and patients with AIDS and other serious illnesses. We also suggest that certain organizational and professional characteristics of nursing and medicine reinforce this tendency to refer to the trials as treatment. Implications for further research are provided.

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Clinical use of Antiviral Drugs

Drug Intelligence & Clinical Pharmacy ◽

10.1177/106002808702100501 ◽

1987 ◽

Vol 21 (5) ◽

pp. 399-405 ◽

Cited By ~ 5

Author(s):

Milap C. Nahata

Keyword(s):

Influenza A ◽

Viral Infections ◽

Antiviral Agent ◽

Antiviral Drugs ◽

Investigational Drug ◽

Virus Infections ◽

Herpes Encephalitis ◽

Herpes Simplex Viruses ◽

Varicella Zoster ◽

Syncytial Virus

Remarkable progress has been made in antiviral chemotherapy. Six approved antiviral drugs are now available for the treatment of various viral infections. Trifluridine, idoxuridine and vidarabine are all effective in patients with herpes keratitis; trifluridine is preferred due to its low toxicity. Acyclovir is the drug of choice in patients with infections due to herpes simplex viruses, including genital herpes, herpes encephalitis, and neonatal herpes, and infections due to varicella-zoster virus. Amantadine is the only drug currently available for prophylaxis and treatment of influenza A, but an investigational drug, rimantadine, appears to be equally effective and less toxic than amantadine. Ribavirin is the most recently approved antiviral agent for the treatment of respiratory syncytial virus infections. Numerous antiviral drugs are being studied in patients with acquired immunodeficiency syndrome. Although currently available drugs have improved our ability to manage a variety of viral illnesses, much needs to be learned about specific dosage guidelines based on the studies of pharmacokinetics, pharmacodynamics, potential adverse effects and viral resistance, and the role of combination therapy to optimize therapy.

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