Biomedical subjects

Peter Harper

Publications and source records attributed to Peter Harper.

29 records · Page 2Linked to original sources

PubMed2002

Influenza vaccination and chemotherapy: a shot in the dark?

Influenza infection is a potential cause of excess morbidity in patients who are immunosuppressed because of haemato-oncological malignancy or its treatment. Therefore vaccination against influenza is recommended in these patient groups. This systematic review of the literature and vaccine manafacturers' data assesses the current levels of knowledge concerning influenza vaccination in this patient group. There is a paucity of data, and the patient groups in the studies are heterogeneous. Serological responses are generally lower than expected in healthy controls and may be critically dependent on the timing of vaccination relative to chemotherapy. Antibody levels considered protective in healthy individuals may not prevent clinical infection in those with malignant disease. There are no data on protection from clinical infection. The vaccine appears to be well tolerated in this patient group. It is reasonable to offer vaccination to patients receiving treatment for haemato-oncological disorders. However, the degree of clinical protection afforded may be inferior to that experienced by healthy individuals. Further trials are warranted to assess the magnitude of benefit and optimal schedules of vaccination.

Antibodies, Viral↗

PubMed2002

Effect of renal impairment on the pharmacokinetics and tolerability of capecitabine (Xeloda) in cancer patients.

PURPOSE: The primary objective of this study was to investigate the influence of renal impairment on the pharmacokinetics of capecitabine and its metabolites in cancer patients. Capecitabine (Xeloda) is an orally administered precursor of 5'-deoxy-5-fluorouridine (5'-DFUR), which is preferentially activated to 5-fluorouracil (5-FU) in tumors. METHODS: A total of 27 patients were enrolled, of whom 24 were evaluable for pharmacokinetics (6 with normal renal function, 8 with mild, 6 with moderate, and 4 with severe renal impairment at baseline). Patients received capecitabine orally at the standard dosing regimen (1250 mg/m(2) capecitabine twice daily for 2 weeks followed by a 1-week rest period). On study days 1 and 14, blood samples were collected to evaluate the pharmacokinetics of capecitabine and its metabolites. The relationship between the area under the plasma concentration-time curve (AUC) and creatinine clearance (CL(CR)) was assessed by log-linear regression analysis. RESULTS: The primary pharmacokinetic parameter with respect to the effect of renal dysfunction was systemic exposure to 5'-DFUR, 5-FU and FBAL determined on study day 14. Renal impairment led to an increase in the systemic exposure to 5'-DFUR and FBAL (23% and 109% increase in AUC, respectively) for a 50% reduction in CL(CR). By contrast, renal impairment may lead to decreased exposure to 5'-DFCR. There was no evidence for an effect of renal impairment on systemic exposure to 5-FU or capecitabine. Renal impairment did not have a major effect on peak concentration (C(max)) or elimination half-life (t(1/2)) of capecitabine, 5'-DFCR, 5'-DFUR, and 5-FU. However, in the case of FBAL, moderate or severe renal impairment caused up to a twofold increase in C(max) and prolongation of t(1/2). All patients with severe renal impairment (four patients) had drug-related grade 3 or 4 adverse-events (AEs) and serious AEs. Patients with moderate renal impairment experienced a similar number of grade 3 or 4 AEs (six of nine patients) but had a higher incidence of serious AEs (three of nine patients) when compared with those with normal renal function (four of six patients and one of six patients, respectively). A similar effect was seen in patients with mild renal dysfunction (grade 3 or 4 AEs in four of eight patients; serious AEs in three of eight patients). The relationship between systemic exposure to capecitabine or its metabolites and safety was investigated using logistic regression. This exploratory analysis showed a strong positive relationship between AUC of 5'-DFUR and treatment-related grade 3 or 4 AEs, whereas there was no relationship with exposure to capecitabine, 5'-DFCR, 5-FU or FBAL. CONCLUSIONS: Renal impairment has no effect on the pharmacokinetics of capecitabine or 5-FU, but leads to an increase in the systemic exposure to 5'-DFUR and FBAL. However, only the AUC of 5'-DFUR is correlated with safety. Based on the safety results in patients with severe renal impairment, a dose modification cannot be recommended for these patients and they should not be treated with capecitabine. Additional data from the clinical safety database and pharmacokinetic results from the present study support the recommendation that patients with moderate renal impairment should be treated with 75% of the recommended standard starting dose to achieve systemic exposure comparable to that in patients with normal renal function.

Antimetabolites, Antineoplastic↗

PubMed2002

Combined modality treatments in early non-small cell lung cancer.

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Adult↗

PubMed2002

Non-platinum gemcitabine combinations in non-small cell lung cancer.

Lung cancer remains the most common cause of cancer related death. Although the primary goal of therapy is improvement in survival, improvement of symptoms, and quality of life are also important. Platinum-based chemotherapy has been shown to confer a modest but statistically significant survival benefit. Platinum-based therapy, however, has been associated with significant toxicity. Newer agents, such as gemcitabine, vinorelbine, paclitaxel, docetaxel, and irinotecan have been introduced into clinical practice. These agents have different mechanisms of activity and improved toxicity profiles. Combinations of these novel agents have been developed in an attempt to improve the toxicity profile and efficacy of the treatment of non-small cell lung cancer. This paper evaluates gemcitabine-based non-platinum combinations in the treatment of non-small cell lung cancer. Ongoing research evaluating the optimal dose, schedule, and combination is important in achieving improved outcomes in terms of survival and quality of life.

Aged↗

PubMed2002

Predictive DNA-testing for Huntington's disease and reproductive decision making: a European collaborative study.

This European collaborative study addresses the question whether a predictive test result for Huntington's disease (HD) has an effect on subsequent reproduction by comparing carriers and non-carriers of the Huntington mutation. A unique characteristic of this study is that this evaluation is done in persons at reproductive age who had a predictive test after the identification of the Huntington gene and who were counselled in one of the participating centres. Data were collected for 180 carriers and 271 non-carriers who received a predictive test result in the period 1993-1998 in Aberdeen, Athens, Cardiff, Leiden, Leuven, Paris or Rome. The mean age of the total study group was 31.5 years and for about half of the group the follow-up interval was 3 years or more, with a maximum of 7 years. The collaborative study clearly revealed an overall impact of the predictive test result on subsequent reproduction: 14% of the carriers had one or more subsequent pregnancies vs 28% of the non-carriers. In the total carrier group a prenatal test was carried out in about two thirds of the pregnancies and one child was born after preimplantation genetic diagnosis; artificial insemination by donor, egg cell donation or adoption were not reported. A more refined analysis was performed in the subgroup with a follow-up interval of at least 3 years and who reported 'family planning' as a motive to apply for predictive testing in the pretest period. The complexity of this motive is discussed. In this subgroup with a desire for children in the pretest period the effect of the predictive test result was more pronounced: 69% of the non-carriers had subsequent pregnancies while only 39% of the carriers who mentioned 'family planning' as one of the major reasons to apply for predictive testing had a subsequent pregnancy. Of the carriers with one or more subsequent pregnancies the percentage using prenatal diagnosis was slightly higher than the percentage not using it, although there were clear differences from one centre to another. The latter group's decisions may seem more intriguing but may be partially understood based on stage theories of health behaviour. Last, but not least, whatever option is chosen by a couple at increased risk of transmitting the Huntington mutation, it is of the utmost importance that professionals fully respect this decision and support the couple.

Adult↗

PubMed2002

Prenatal testing for Huntington's disease: a European collaborative study.

This European study involving seven genetic centres from six countries - Aberdeen, Cardiff (UK), Leiden (Netherlands), Leuven (Belgium), Paris (France), Rome (Italy), Athens (Greece) has gathered information on prenatal testing by direct mutation analysis and exclusion testing for Huntington's disease (HD) from the six European countries during the period 1993-1998. Data describing the parent belonging to the HD family was collected; this included their sex and age as well as their risk of developing HD. Information about previous pregnancies, the rank of the pregnancy being tested and its outcome was also gathered. In addition the number of previous prenatal tests for HD was recorded. Three hundred and five results were recorded by the participating countries between 1993 and 1998. The largest groups came from the UK (157) and the Netherlands (90). The mean age for the parent from the HD family was 30.8 years. In half of the tests the prospective parent was an asymptomatic gene carrier, 42% remained at risk, and 6% of the prospective parents were already showing clinical features of HD. 65% of tests performed used mutation analysis.

Adolescent↗

PubMed2002

Current clinical practices for ovarian cancers.

Ovarian cancer is one of the most aggressive gynecologic cancers. It shows its symptoms late and is consequently often diagnosed at an advanced stage. The search for a more effective chemotherapy regimen, therefore, is of great importance. Since 1996, the combination of cisplatin and paclitaxel has been proven to prolong survival in comparison with older regimens containing cisplatin and cyclophosphamide. In addition, the introduction of carboplatin in combination with paclitaxel showed similar efficacy but preferable toxicity profiles when compared with cisplatin in combination with paclitaxel. Representative studies evaluating paclitaxel combination therapies as well as new trends in the treatment of ovarian cancer are summarized in this article.

Anemia↗

PubMed2002