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Biomedical subjects

P G Harper

Publications and source records attributed to P G Harper.

At least 19 recordsLinked to original sources
PubMed1997

Five-day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy.

BACKGROUND: Oral etoposide is an active single agent in small-cell lung cancer (SCLC) and is widely prescribed as first-line treatment as an alternative to intravenous combination chemotherapy in patients with extensive disease. PURPOSE: The intention of this study was to determine if the effects of oral etoposide therapy on survival and quality of life are equivalent to those of intravenous chemotherapy. METHODS: In a randomized trial of palliative treatment in advanced SCLC, oral etoposide (100 mg given twice daily for 5 days) was compared with intravenous chemotherapy consisting of alternating cycles of cisplatin and etoposide (PE) and cyclophosphamide, doxorubicin, and vincristine (CAV). Six cycles of chemotherapy were administered every 21 days in both regimens. Symptom control and quality of life were measured with the Rotterdam Symptom Checklist and a daily diary card. In January 1996, after 155 patients had been randomly assigned from a projected intake of 365 patients, an independent Data Monitoring Committee examined the interim results. Survival was determined by the Kaplan-Meier method, and the logrank test was used to compare treatments. For quality-of-life comparisons, average scores were calculated for each time point. The Mann-Whitney U test was used to determine any significant overall differences between treatments. For the Rotterdam Symptom Checklist, separate analyses were done for each subset (psychological well-being, physical symptoms, lung cancer symptoms, treatment symptoms, activity, and quality of life). Response rates and toxicity scores were compared by using chi2. All statistical tests were two-sided. RESULTS: Survival was inferior at 1 year in the oral etoposide group compared with intravenous therapy (9.8% for oral versus 19.3% for intravenous; difference = 9.5%; 95% confidence interval of difference = 0.3%-18.7%; P<.05), and there was a trend toward inferior overall survival. Median survival was 4.8 months for oral treatment and 5.9 months for intravenous therapy. Progression-free survival was worse in the oral etoposide arm (median = 3.6 months versus 5.6 months; P<.001), as well as overall response rate (32.9% versus 46.3%; P<.01). With the exception of acute nausea and vomiting associated with intravenous chemotherapy, all aspects of symptom control and quality of life were either the same or worse in the oral etoposide group. Study closure was recommended. CONCLUSIONS: These interim results show that this schedule of oral etoposide is inferior to intravenous chemotherapy in the treatment of advanced SCLC and should not be used as first-line treatment of this disease.

Administration, Oral↗
PubMed1996

Partitioning of ifosfamide and its metabolites between red blood cells and plasma.

A recently developed GC-MS analytical method for the quantitative determination of oxazaphosphorines and their metabolites in blood plasma, using stable trifluoroacetyl derivatives and electron capture negative chemical ionization detection, was applied to measure the partitioning of the antitumor drug ifosfamide and its metabolites between plasma and red blood cells for four cancer patients. The separation of a constant volume of red blood cells was performed using a special instrument, MESED, through centrifugation of blood samples. The measured compounds were ifosfamide, 2- and 3-dechloroethylifosfamide, 4-ketoifosfamide, carboxyifosfamide, ifosfamide mustard, 2-chloroethylamine and 1,3-oxazolidin-2-one. Concentration-time profiles for the metabolites in the two blood fractions and partitioning factors between erythrocytes and plasma were obtained. For ifosfamide itself, and metabolites with an intact ring system, a partitioning factor between 1 and 2 was observed for the concentration ratio between red blood cells and plasma in the patients studied. However, for the compounds with an open structure, carboxyifosfamide and ifosfamide mustard, partitioning factors higher than 3 were obtained. The active antitumor metabolite ifosfamide mustard showed a strong preference for the red blood cells in the measured patient samples. This means that erythrocytes may play an important role in the transport and the subsequent release of the active alkylating agent to the tumor cells.

Erythrocytes↗
PubMed1996

A randomised trial of low-dose/high-frequency chemotherapy as palliative treatment of poor-prognosis small-cell lung cancer: a Cancer research Campaign trial.

We report the results of a randomised trial in extensive small-cell lung cancer (SCLC) of a novel approach to palliative chemotherapy. A widely used 3 weekly regimen was compared with the same drugs given at half the dose but twice the frequency with the same intended overall dose intensity (DI). A total of 167 patients defined as having extensive SCLC with adverse prognostic features were randomised to receive either a 3 weekly regimen of cisplatin 60 mg m-2 i.v. on day 1 and etoposide 120 mg m-2 i.v. on day 1 and 100 mg b.d. orally on days 2 and 3 alternating with cyclophosphamide 600 mg m-2 i.v., doxorubicin 50 mg m-2 i.v. and vincristine 2 mg i.v. all on day 1 for a maximum of six courses (3 weekly); or treatment with the same drugs but with each course consisting of half the 3 weekly dose given every 10 or 11 days for a maximum of 12 courses. In the 10/11 day regimen overall response rate was 58.9% (95% CI, 47.9-69.2%) with 12.8% complete responses (CR). For the 3 weekly treatment the overall response rate was 44.9% (95% CI, 35.0-55.5%) with 10.1% CR. Median survival was similar in the two arms at 6.4 months (95% CI, 4.9-7.3 months) and 5.8 months (95% CI, 4.0-6.6 months) respectively. Survival at 1 year was 9.9% (95% CI, 5.0-18.5%) and 8.9% (95% CI, 4.6-16.6%). The 95% CI for the difference in survival at 1 year is -7.09% to +9.09%. Haematological toxicity and treatment delays owing to infection were more frequent with the 10/11 day regimen but other toxicities were equal in both arms. Other aspects of quality of life were measured in a small representative cohort of patients using a daily diary card (DDC). There was a trend of improved quality of life on the 10/11 day arm, but there was little difference between the two treatments. The trial shows that a low-dose/high-frequency regimen with the same DI as conventionally scheduled chemotherapy gives similar response rates and survival. This and other modifications of the schedule may offer new approaches to palliative treatment of advanced cancer. However, in this trial there was no significant benefit in toxicity or other aspects of quality of life.

Adult↗
PubMed1996

Randomized trial assessing the addition of interferon alpha-2a to fluorouracil and leucovorin in advanced colorectal cancer. Colorectal Cancer Working Party of the United Kingdom Medical Research Council.

PURPOSE: To determine the effects of interferon alpha-2a (IFN alpha) on the efficacy and toxicity of fluorouracil (FUra) and leucovorin (LV) in patients with advanced colorectal cancer. PATIENTS AND METHODS: Two hundred sixty chemotherapy-naive patients were randomized to FUra/LV alone or FUra/LV plus IFN alpha. All patients received: LV 200 mg/m2 intravenous (IV) infusion over 2 hours, then FUra 400 mg/m2 i.v. bolus plus 400 mg/m2 i.v. infusion over 22 hours, all repeated on day 2. Treatment was every 2 weeks for up to 12 cycles. Patients randomized to IFN alpha received 6 x 10(6) IU subcutaneously every 48 hours throughout. Objective response (OR) and toxicity were assessed conventionally; in addition, palliative benefit and adverse effects were assessed using quality-of-life (QoL) questionnaires. RESULTS: There were no differences in OR rate, progression-free survival, or overall survival. OR rates in assessable patients were as follows: FUra/LV alone (n = 104), complete or partial response (OR) = 27%, no change (NC) = 34%; FUra/LV/IFN alpha (n = 101), OR = 28%, NC = 30%. Median survival was 10 months in both arms. Dose-limiting FUra toxicities were not significantly increased by co-administration of IFN alpha, and the delivered FUra dose-intensity was not significantly reduced. However, QoL was adversely affected: patients on IFN alpha were less likely to report improvement in pretreatment physical and psychologic symptoms, and more likely to report new or worsening symptoms. CONCLUSION: IFN alpha, at a dose that impaired QoL, did not improve the efficacy of FUra/LV. The power of this trial is sufficient to exclude with 95% confidence a benefit of 15% in OR or 10 weeks in median survival. Accordingly, we cannot recommend the use of IFN alpha as a clinical modulator of FUra/LV in the treatment of advanced colorectal cancer.

Adult↗
PubMed1995

Use of a 'Health Habits Questionnaire' to improve health promotion counseling.

A 10-item patient "Health Habits Questionnaire" was developed that included counseling topics recommended by the US Preventive Services Task Force. Patient education brochures for each of these topics were designed and displayed in examination rooms. The questionnaires were to be given to every adult presenting to a family medicine residency clinic for a physical examination. Charts of patients receiving physical examinations were audited. Of 368 visits, 206 questionnaires were completed. Patients who completed the questionnaires were significantly more likely to have chart documentation of counseling about seat-belt use, exercise, stress, alcohol and other drug use, and dental health. The topic areas that had no significant improvement in documentation had higher counseling documentation rates than those that improved. The Health Habits Questionnaire appears to be a useful tool to improve counseling documentation, particularly for those habits that may otherwise receive little counseling.

Adult↗
PubMed1995

Gender affects doxorubicin pharmacokinetics in patients with normal liver biochemistry.

We studied the variability in doxorubicin pharmacokinetics in 27 patients, all of whom had normal liver biochemistry tests. Blood samples were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by high-performance liquid chromatography (HPLC). The relationship of doxorubicin clearance (dose/AUC) with biochemical tests (AST, bilirubin, alkaline phosphatase, albumin, creatinine) and physical characteristics (age, gender, height, weight, tumour type) was investigated. The 6 men had a significantly higher doxorubicin clearance than did the 21 women (median values, 59 and 27 lh-1 m-2, respectively; P = 0.002). Doxorubicin clearance was significantly lower in patients with breast cancer than in those with other tumours (median values, 26 and 53 lh-1 m-2, respectively; P = 0.0008). The other biochemical and physical parameters did not correlate with doxorubicin clearance. However, in multivariate analysis, gender was the only factor predicting doxorubicin clearance (r2 = 40%). The ratio of the AUCs for doxorubicinol and doxorubicin (R) was higher in the men than in the women (median values, 0.62 and 0.36, respectively; P = 0.03). We conclude that gender may be an important determinant of doxorubicin clearance in patients with normal liver biochemistry.

Adult↗
PubMed1995

Phase II trial of temozolomide in low-grade non-Hodgkin's lymphoma.

Temozolomide, an imidazotetrazine derivative, was given to 18 patients with low-grade non-Hodgkin's lymphoma (NHL) at a dose of 750 mg m-2 orally, divided over five consecutive days, escalated to 1000 mg m-2 over 5 days (i.e. 200 mg m-2 day-1) if no significant myelosuppression was noted at day 22 of the 28 day cycle. Fifty-six treatment cycles were given to 18 patients. The drug was well tolerated. Only one partial tumour response was documented. The patients were heavily pretreated but had chemoresponsive disease, as shown by a response rate of 69% among 13 patients who went on to receive alternative cytotoxic regimens. We conclude that temozolomide given in this schedule is inactive in previously treated low-grade NHL.

Adult↗
PubMed1995

Assessment of 'quality of life' using a daily diary card in a randomised trial of chemotherapy in small-cell lung cancer.

BACKGROUND: Quality of life (QOL) was assessed using a daily diary-card within a multicentre randomised trial of treatment of small-cell lung cancer. The trial compared a weekly dose-intensive regimen with a 3-weekly conventional treatment in good prognosis patients, that is patients with limited disease or extensive disease with a good performance status (ECOG 0or 1) and alkaline phosphatase of less than one and a half times the upper limit of normal. The trial which has been previously reported detected no difference in response or survival. PATIENTS AND METHODS: Daily diary cards (DDCs) were collected for up to eight months from the first day of chemotherapy in a cohort of 75 patients at one centre. Percentages of scores over a specified level were calculated for each of the eight diary card questions and comparisons were made between treatment arms. RESULTS: During the period of chemotherapy compliance in completing DDCs was 72.5% in the weekly arm and 77.2% in the 3 weekly. Significantly worse scores were reported with weekly chemotherapy during this period for six of the eight parameters, namely: ;nausea, vomiting, happiness, appetite, general well-being and sleep. Recognised problems of QOL data collection, in particular, compliance, attrition and generalisability are highlighted by this study and are discussed in the paper. CONCLUSIONS: The QOL measurements indicate that 3 weekly chemotherapy is the preferred treatment. This study demonstrates that QOL measurements may be helpful in choosing between treatment alternatives where no difference in outcome is observed.

Adult↗
PubMed1994

An organizational strategy to improve adolescent measles-mumps-rubella vaccination in a low socioeconomic population. A method to reduce missed opportunities.

OBJECTIVE: To determine whether a clinical organization strategy can improve measles-mumps-rubella vaccination rates in adolescents by reducing missed opportunities. DESIGN: Nonequivalent control group design with a treatment clinic and a comparison clinic. Measurements were made for 8 months before intervention and for 9 months after intervention. SETTING: Two urban family practice clinics serving a low socioeconomic population. POPULATION: All clinic visits by adolescents aged 11 to 18 years. INTERVENTION: A clinic organizational strategy that systematically identified and vaccinated adolescents seen in the clinic for any reason. MAIN OUTCOME MEASURES: Two vaccination indexes were measured monthly at each clinic: the percentage of eligible visits at which measles-mumps-rubella vaccination was given and the percentage of visits that were up to date, with adolescents having received the measles-mumps-rubella vaccine at that visit or at a previous visit. RESULTS: The intervention resulted in a significant increase at the treatment clinic in the mean percentage of vaccinations given (from 7.8% to 17.4%) (Student's t = 3.02; P = .0087) and the mean percentage of up-to-date visits (from 17.2% to 38.6%) (t = 8.33; P < .0001). During the same period, there was no significant change in the mean vaccination rates in the comparison clinic. CONCLUSIONS: An organizational strategy appears to be a useful method to reduce missed opportunities and improve measles-mumps-rubella vaccination rates in adolescents from a low socioeconomic population.

Adolescent↗
PubMed1994

Too many shots? Parent, nurse, and physician attitudes toward multiple simultaneous childhood vaccinations.

OBJECTIVE: To learn about parent, nurse, and family physician attitudes toward multiple simultaneous childhood vaccinations. DESIGN: Survey. SETTING: Thirty-two family practice clinics in Minnesota. PATIENTS/PARTICIPANTS: Forty-six volunteer Minnesota Academy of Family Physicians Research Network members, 42 of their nurses, and 342 parents of their patients aged less than 6 years who have had at least one injection. MAIN OUTCOME MEASURES: Number of injections believed to be too many for a child to receive simultaneously and comfort level associated with children's receiving three simultaneous injectable vaccinations. RESULTS: Most parents, nurses, and physicians (71%, 76%, and 59%, respectively) think that three injections are too many for a child to receive at one visit. Similar percentages of parents, nurses, and physicians are uncomfortable with a child's receiving three injections at one visit. Sixty-seven percent of the physicians who do not offer universal newborn hepatitis B vaccinations cite the number of required simultaneous injections as a factor in that decision. Only 15% of physicians order all three recommended injections for most of their 15-month-old patients. CONCLUSIONS: Most parents, nurses, and physicians are uncomfortable with three simultaneous injections for children. This discomfort may be a significant barrier to the adoption of the new immunization recommendations. The development of effective combination vaccines should be a research priority.

Adult↗
PubMed1994

Combination chemotherapy with epirubicin, cisplatin and 5-fluorouracil for the palliation of advanced gastric and oesophageal adenocarcinoma.

The palliative efficacy of laser therapy with combination chemotherapy (cisplatin, epirubicin and continuous infusion of 5-fluorouracil) was assessed in 34 patients with inoperable gastro-oesophageal cancer. Comparison was made with a group of 30 patients treated previously by laser alone. Twenty patients responded to chemotherapy. There was a significant improvement in dysphagia, as measured by a decreased laser requirement to maintain satisfactory swallowing. In this non-randomized prospective phase II trial, palliation was attained and some responses were long-lasting (median duration of response 8.7 (range 2.3 to more than 29.2) months).

Adenocarcinoma↗
PubMed1994

Health promotion counseling in residency training.

This report describes health promotion counseling attitudes and practices in a family medicine residency that attempted to encourage such counseling. A patient "Health Habits Questionnaire" and matching patient education booklets were developed and distributed. Six grand rounds presentations on counseling were given. On three occasions, residency physicians completed questionnaires about counseling. Despite good personal health habits and positive attitudes toward counseling, the residency physicians had only moderate confidence in their counseling ability and infrequently documented counseling. The residents reported significant improvement in their ability to counsel patients about smoking cessation. Overall, the curriculum appeared to have a limited effect on health promotion.

Adult↗
PubMed1994

Protracted oral etoposide in epithelial ovarian cancer: a phase II study in patients with relapsed or platinum-resistant disease.

This phase II study evaluates the efficacy and toxicity of a prolonged schedule of oral etoposide in patients with measurable advanced ovarian cancer resistant to, or relapsed following, platinum-based chemotherapy. Forty-seven patients participated, 20 of whom had received more than one prior treatment. Seventy-seven per cent had evidence of disease progression during or within 6 months of the previous chemotherapy. Initially, oral etoposide, 50 mg b.d. (regardless of patient size), was given for 14 days on a 21-day cycle. However, after encountering toxicity, the schedule was modified to 7 days' treatment escalating to 10 then 14 days if well tolerated. Among 41 assessable patients there were two complete and eight partial objective responses (24% response rate; 95% confidence interval 12-41%). Nine further patients (22%) had stable disease, four with a sustained fall of > 50% in CA-125. Median duration of response or stable disease was 35 weeks (range 21-49). Overall median survival was 41 weeks from study entry (range 2 to 96+ weeks). Toxicity for most patients was mild, but sporadic severe myelotoxicity occurred, with two treatment-related deaths. Risk factors for severe toxicity were: performance status 3; hepatic impairment; renal impairment. We conclude that oral etoposide has activity in platinum-resistant ovarian cancer and that it is a useful palliative therapy. It has significant toxicity which may be avoided by appropriate patient selection and an escalating-duration schedule.

Administration, Oral↗
PubMed1994

Received dose-intensity: a randomized trial of weekly chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer.

PURPOSE: A prospective randomized trial to determine if granulocyte colony-stimulating factor (G-CSF) could increase the received dose-intensity (RDI) of weekly chemotherapy in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Forty patients with SCLC with good prognostic features (all patients with limited disease [LD], and extensive-disease [ED] patients with Eastern Cooperative Oncology Group [ECOG] 0 or 1 and plasma alkaline phosphatase levels < 1.5 times the upper limit of normal) were randomized to receive weekly chemotherapy with or without G-CSF. G-CSF (5 micrograms/kg) was self-administered subcutaneously on days when chemotherapy was not given. Chemotherapy consisted of cisplatin 50 mg/m2 intravenously (IV) on day 1 and etoposide 75 mg/m2 IV on days 1 and 2 alternating weekly with ifosfamide 2 g/m2 IV (with mesna) and doxorubicin 25 mg/m2 on day 1, for a total of 12 courses. Dose modifications (dose reductions and treatment delays) were made according to defined hematologic criteria. RESULTS: Dose reductions were made at some point during treatment in 12 of 17 patients in the control arm and in 11 of 23 patients in the G-CSF arm (P = .20). The proportion of patients experiencing dose reductions due to leukopenia was significantly higher in the control arm (nine of 17) compared with the G-CSF arm (four of 23, P < .04). Cycle delays due to leukopenia were similar in both arms of the study. The RDI was 82% of projected in the control arm (95% confidence interval [CI], 79% to 84%) and 84% in patients receiving G-CSF (95% CI, 82% to 87%) (P value not significant). CONCLUSION: In this randomized trial, G-CSF significantly decreased dose reductions due to neutropenia. However, administration of G-CSF did not decrease dose reductions or treatment delays to a level that would allow an increase in received dose-intensity. Nonhematologic toxicities such as increased creatinine concentration also prevented an increase in the RDI in the G-CSF arm.

Adult↗