Tumor physiology and resistance to chemotherapy: repopulation and drug penetration.
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Antineoplastic Agents↗
Biomedical subjects
Ian F Tannock
Publications and source records attributed to Ian F Tannock.
"PSA-itis": knowledge of serum prostate specific antigen and other causes of anxiety in men with metaststic prostate cancer.
PURPOSE: High or increasing prostatic specific antigen (PSA) levels may be a source of anxiety in patients with metastatic prostate cancer. MATERIALS AND METHODS: Patients with metastatic prostate cancer completed questionnaires, including the Prostate Cancer Specific Quality of Life Instrument, Hospital Anxiety and Depression Scale, and a questionnaire to assess the impact of the knowledge of PSA levels on anxiety. These were completed at home more than 3 days before or after a clinic appointment and returned by mail. Patient medical history was obtained from the record. RESULTS: Of the 65 patients who consented to the study 52 returned the completed questionnaires. Median age was 70 years (range 55 to 86) and median time since diagnosis was 53 months. Of the patients 81% had hormone resistant disease. Most reported good overall quality of life with a median Prostate Cancer Specific Quality of Life Instrument score of 93 (maximum 100). Of the patients 77% indicated that PSA levels were one of the ways and 44% indicated they were the only way that they knew whether disease was progressing. When asked to rate preferences for treatment outcome, 25% of the men rated decreasing PSA and worse physical symptoms above increasing PSA and better physical symptoms. If measurement of PSA levels ceased, 52% of patients would believe that their doctor was giving up on them and only 1 would be relieved. Before receiving PSA results 76% reported some level of anxiety and 15% reported extreme anxiety. CONCLUSIONS: PSA related anxiety represents a substantial problem in patients with metastatic prostate cancer.
Affect↗
The role of systemic chemotherapy in the management of muscle-invasive bladder cancer.
Patients with localised but muscle-invasive transitional-cell carcinoma (TCC) of the bladder are at high risk of relapse and death from metastatic disease after local treatment by cystectomy, radiation, or both. Despite improvements in treatment, patients with metastatic TCC have a median survival of about a year. TCC is quite sensitive to chemotherapy, and patients are able to tolerate newer regimens such as gemcitabine plus cisplatin better than older regimens such as methotrexate, vinblastine, doxorubicin, and cisplatin. However, the role of chemotherapy in the management of locally advanced muscle-invasive TCC remains uncertain. Most trials of neoadjuvant or adjuvant chemotherapy have shown no significant improvement in survival, but many of these studies had suboptimum design, evaluated chemotherapy that was less effective than regimens in current use, and had sample sizes that were too small for important changes in survival to be detected or ruled out. Recent trials show trends in the direction of improved survival when optimum chemotherapy is used. Large trials that recruit more than 1000 patients are required to assess the effectiveness of adjunctive chemotherapy, and a large intergroup trial is in progress. Other trials should address the role of molecular markers in selecting patients for chemotherapy. Whenever possible, chemotherapy for locally advanced muscle-invasive TCC should be given in the context of a well-designed clinical trial.
Antineoplastic Combined Chemotherapy Protocols↗
Doctor's dilemma: incorporating tumor markers into clinical decision-making.
Physicians are often faced with the dilemma of how to incorporate tumor markers into routine clinical decision-making. Tumor markers may influence clinical decisions at various stages of cancer therapy: screening, diagnosis, prognosis, detection of early relapse, and monitoring of therapy. We use the examples of beta-human chorionic gonadotrophin (beta-HCG) and alpha-fetoprotein (AFP) as markers for germ cell tumors (GCT), and prostate-specific antigen (PSA) as a marker for prostate cancer, to illustrate their use and limitations for these purposes. We then focus on monitoring and choice of treatment by presenting three vignettes; these highlight the potential benefits and problems associated with the use of tumor markers for monitoring and detection of early relapse in asymptomatic patients.
Adult↗
Limited penetration of anticancer drugs through tumor tissue: a potential cause of resistance of solid tumors to chemotherapy.
PURPOSE: Potential causes of drug resistance in solid tumors include genetically determined factors expressed in individual cells and those related to the solid tumor environment. Important among the latter is the requirement for drugs to penetrate into tumor tissue and to achieve a lethal concentration in all of the tumor cells. The present study was designed to characterize further the multicellular layer (MCL) method for studying drug penetration through tumor tissue and to provide information about tissue penetration for drugs used commonly in the treatment of human cancer. EXPERIMENTAL DESIGN: EMT-6 mouse mammary and MGH-U1 human bladder cancer cells were grown on collagen-coated semiporous Teflon membranes to form MCLs approximately 200 microm thick. The properties of MCLs were compared with those of tumors grown in mice from the same cells. The penetration of drugs through the MCL was evaluated by using radiolabeled drugs or analytical methods. RESULTS: The MCL developed an extracellular matrix containing both laminin and collagen, although there were some differences in expression of extracellular matrix proteins. Electron microscopy showed rare desmosomes in both MCL and tumors. The penetration of cisplatin, etoposide, gemcitabine, paclitaxel, and vinblastine through tissue in the MCL was slow compared with penetration through the Teflon support membrane alone. CONCLUSIONS: Our results suggest limited ability of anticancer drugs to reach tumor cells that are distant from blood vessels. The limited penetration of anticancer drugs through tumor tissue may be an important cause of clinical resistance of solid tumors to chemotherapy.
Animals↗