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Biomedical subjects

M J Boyer

Publications and source records attributed to M J Boyer.

At least 19 recordsLinked to original sources
PubMed2006

Disarming the guarded prognosis: predicting survival in newly referred patients with incurable cancer.

People affected by cancer want information about their prognosis but clinicians have trouble estimating and talking about it. We sought to determine the nature and accuracy of medical oncologists' estimates of life expectancy in newly referred patients with incurable cancer. With reference to each patient, medical oncologists estimated how long they thought 90, 50, and 10% of similar patients would live. These proportions were chosen to reflect worst case, predicted, and best case scenarios suitable for discussions. After a median follow-up of 35 months, 86 of the 102 patients had died with an observed median survival of 12 months. Oncologists' estimates of each patient's worst case, predicted and best case scenarios were well-calibrated: 10% of patients lived for fewer months than estimated for the worst 10% of similar patients; 50% lived for at least as long as estimated for 50% of similar patients (predicted survival), and 17% lived for more months than estimated for the best 10% of similar patients. Oncologists' estimates of each patient's predicted survival were imprecise: 29% were within 0.67-1.33 times the patient's actual survival, 35% were too optimistic (>1.33 times the actual survival), and 39% were too pessimistic (<0.67 times the actual survival). The proportions of patients with actual survival times bounded by simple multiples of their predicted survival were as follows: 61% between half to double their predicted, 6% at least three to four times their predicted, and 4% no more than 1/6 of their predicted; similar to the proportions in an exponential distribution (about 50%, 10% and 10% respectively). Ranges based on simple multiples of the predicted survival time appropriately convey prognosis and its uncertainty in newly referred people with incurable cancer.

Adolescent↗
PubMed2005

Smoking reduction does work: resulting alterations in the incidence and histological subtypes of lung cancer in New South Wales in the last 20 years.

BACKGROUND: There is irrefutable evidence of the association between lung cancer and smoking. The effects of public health campaigns to reduce population-smoking rates on the incidence and the histological distribution of lung cancer were examined. METHODS: The data held in the New South Wales Cancer Registry from 1972 to 2001 was accessed. RESULTS: The data revealed a decreasing incidence of lung cancer amongst males and a rate that continued to increase amongst females. Interestingly, there was also an effect on the histological distribution of lung cancers, with falling rates of small cell lung cancer and squamous cell cancer, both of which have a high association with smoking; and an increasing incidence of adenocarcinomas. CONCLUSIONS: These trends reveal patterns seen worldwide. The increasing proportion of adenocarcinomas in particular may be related to the changing composition of cigarettes and filters.

Carcinoma, Small Cell↗
PubMed2005

Weekly docetaxel as second line treatment after mitozantrone for androgen-independent prostate cancer.

BACKGROUND: Two recent phase III trials have shown an improvement in survival with the use of docetaxel in metastatic androgen-independent prostate cancer (AIPC) compared to mitozantrone. However no phase II trials have clearly defined the level of activity of docetaxel after mitozantrone. AIMS: We sought to define the activity and toxicity of weekly docetaxel as second line chemotherapy after mitozantrone in men with AIPC. METHODS: Twenty men were treated with docetaxel 40 mg/m2 weekly for 3 of every 4 weeks until progression or prohibitive toxicity. End-points included prostate specific antigen response, common toxicity criteria, time to progression and overall survival. RESULTS: Nine patients (45%) had a 50% or greater reduction in PSA maintained for at least 1 month. Weekly docetaxel was well tolerated with few major toxicities: two patients had Grade 3 diarrhoea (10%) and six had grade 2-4 haematologic toxicities (30%). The median time to progression was 5 months (range 0-13) and median survival was 13 months (range 1-24) from starting docetaxel. The median survival from starting mitozantrone was 19 months. Men who had responded to mitozantrone were no more likely to respond to docetaxel (P = 0.2 Fischer's exact test). CONCLUSIONS: Weekly docetaxel is a safe and active second-line treatment after mitozantrone for androgen-resistant prostate cancer, with similar levels of activity to the first-line setting.

Adenocarcinoma↗
PubMed2003

Docetaxel and carboplatin is an active regimen in advanced non-small-cell lung cancer: a phase II study in Caucasian and Asian patients.

BACKGROUND: The purpose of this study was to report response rates, survival and toxicity in advanced non-small-cell lung cancer (NSCLC) following docetaxel and carboplatin, and to explore potential differences in these end points between Caucasian and Asian patients. PATIENTS AND METHODS: Sixty-eight patients of good performance status with Stage IIIB or IV NSCLC were entered on a phase II study at three sites in Australia and Singapore. Docetaxel 75 mg/m2 and carboplatin AUC 6 were given every 3 weeks. Response to treatment and toxicity were graded by standard criteria. The Kaplan-Meier method was used to estimate survival rates, and subgroups compared by the log-rank test. Cox's proportional hazards regression was used to determine which potentially explanatory variables independently affected the outcome. RESULTS: The response rate was 39% (95% confidence interval 27% to 52%), and 42% in evaluable patients. Response occurred in 65% of Asian and 31% of Caucasian patients (P = 0.01). Ethnicity was the only significant predictor of response in multivariate analysis. The 1-year survival rate was 53%. Performance status (P = 0.021), ethnicity (P = 0.035) and presence of bone or liver metastases (P = 0.011) were independent predictors of overall survival. Neutropenia (grade IV in 73% of patients), febrile neutropenia (26% patients) and diarrhea (grade III/IV in 11% of patients) were the major treatment related toxicities. A high rate (three of six) of febrile neutropenia in Singapore, including one treatment-related death in the initial patients treated, resulted in a reduction in the carboplatin dose to AUC 4.5 at that site. CONCLUSIONS: This regimen is active in advanced NSCLC. The potential impact of ethnicity on efficacy and toxicity of treatment requires further investigation.

Adult↗
PubMed2002

Phase II trial of pemetrexed disodium (ALIMTA, LY231514) in chemotherapy-naïve patients with advanced non-small-cell lung cancer.

BACKGROUND: To evaluate the efficacy and safety of pemetrexed therapy for chemotherapy-naïve patients with surgically incurable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients received pemetrexed 600 mg/m2 every 3 weeks. Restaging was performed after every two cycles of therapy and toxicity was assessed at each cycle of pemetrexed. In the absence of disease progression or undue toxicity, treatment was continued for a maximum of 12 cycles. RESULTS: Fifty-nine patients (median age 59 years; range 39-74 years) received a median of four cycles of pemetrexed. Nineteen patients (32%) had a ECOG performance status (PS) of two and 39 patients (66%) had stage IV disease. The most common histological sub-types were adenocarcinoma (20 patients, 34%) and large cell (18 patients, 31%). Sixteen patients (27%) had received prior radiotherapy. Nine patients achieved a partial response for an overall response rate of 15.8% (95% confidence interval CI 7% to 28%). The median duration of response was 4.9 months, and the median survival was 7.2 months. The principal toxicities were myelosuppression and rash. While grade 3 or 4 neutropenia was seen in 25 patients (42%), only two patients (3%) developed grade 3 infection. Eighteen patients (31%) developed grade 3 or 4 cutaneous toxicity, which improved with prophylactic oral dexamethasone administered for 3 days beginning the day before pemetrexed treatment. Asymptomatic elevations in hepatic biochemistry (especially alanine transaminase and aspartate transaminase) were seen in 47 patients (80%); however, these did not interfere with the dose or schedule of pemetrexed and returned to normal levels throughout the study. CONCLUSIONS: This is the largest study confirming the encouraging single-agent activity of pemetrexed in chemotherapy-naïve patients with NSCLC. In addition, this study demonstrates that a dose of 600 mg/m2 can be delivered safely; however, treatment should be restricted to patients with a PS of 0 or 1. The results of combination studies are awaited with interest.

Adult↗
PubMed2002

Resection of residual pulmonary masses after chemotherapy in patients with metastatic non-seminomatous germ cell tumours.

BACKGROUND: Resection of residual post-chemotherapy pulmonary masses in patients with non-seminomatous germ cell tumours gives therapeutic benefit and prognostic information. AIM: This study was undertaken to review the experience of this intervention in a single teaching hospital. METHODS: The Germ Cell Database of the Sydney Cancer Centre was searched for all patients who had undergone excision of pulmonary metastases. These patient records were subsequently reviewed. RESULTS: Between 1976 and 1999, 15 patients underwent a combined total of 19 thoracotomies for resection of residual tumour mass after cisplatin-based chemotherapy. The primary tumour histology included mature teratoma in 47% (7 of 15) of patients. Prior to chemotherapy, 73% (11 of 15) of patients had elevated serum levels of alpha-fetoprotein (median 180 ng/mL) and 60% (9 of 15) of patients had elevated beta-human chorionic gonadotropin (median 672 IU/L). The median length of hospital stay related to thoracotomy was 7 days. There were two surgical complications, a prolonged air leak and a residual pleural effusion. Pathology of residual pulmonary masses revealed necrosis alone in 37% (7 of 19) of procedures, mature teratoma alone in 32% (6 of 19) of procedures and viable tumour in 32% (6 of 19) of procedures. Of those with viable tumour, three achieved long-term complete response (CR), two died of progressive disease (PD) and one is alive with PD. Of those with teratoma, two achieved CR and one relapsed. The long-term CR rate was 80% (12 of 15 patients). The median follow up was 10 years (range 0.75-17.5 years). Four patients died, two of PD and two of cardiovascular disease while in CR. CONCLUSION: At this institution, thoracotomy for residual pulmonary masses was well tolerated, with a high cure rate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomised trial. Australian and New Zealand Germ Cell Trial Group.

BACKGROUND: Most patients with metastatic germ-cell tumours are cured with chemotherapy. However, the optimum chemotherapy regimen is uncertain, and there is variation in international practice. We did a multicentre randomised trial to compare two standard chemotherapy regimens for men with good-prognosis germ-cell tumours. METHODS: Good prognosis was defined by modified Memorial Sloan-Kettering criteria. The first regimen (regimen A) was based on treatment recommendations from Indiana University and comprised three cycles of 20 mg/m2 cisplatin on days 1-5, 100 mg/m2 etoposide on days 1-5, and 30 kU bleomycin on days 1, 8, and 15, repeated every 21 days. The second regimen (regimen B) was based on the control regimen of a published randomised clinical trial and comprised four cycles of 100 mg/m2 cisplatin on day 1, 120 mg/m2 etoposide on days 1-3, and 30 kU bleomycin on day 1, repeated every 21 days. The primary outcome measure was overall survival. Analysis was by intention to treat. FINDINGS: 166 patients were randomised, 83 to each regimen. The trial was stopped when the second planned interim analysis met predefined stopping rules. The median follow-up was 33 months. Overall survival was substantially better with regimen A (three vs 13 deaths, hazard ratio 0.22 [95% CI 0.06-0.77], p=0.008). This difference was due to deaths from cancer (one vs nine), and not deaths from treatment (two vs two) and remained significant after adjustment for other prognostic factors (0.25 [0.07-0.88], p=0.03). INTERPRETATION: In men with good-prognosis germ-cell tumours, the regimen developed at Indiana University is superior to the alternative regimen studied in this trial. The lower total dose and dose-intensity of bleomycin and the lower dose-intensity of etoposide in regimen B could be responsible for the worse outcome.

Adolescent↗
PubMed2001

Phase II study of paclitaxel and oral etoposide in patients with locally advanced or metastatic non-small cell lung cancer.

The combination of paclitaxel and etoposide was evaluated in a phase II study in patients with locally advanced or metastatic non small-cell lung cancer (NSCLC). Thirty-five patients, median age 61, received treatment with paclitaxel 200 mg/m (2) intravenous over 3 h on day 1, and oral etoposide, 100 mg daily on days 1-5. Cycles were repeated every 21 days for a maximum of nine cycles, or until progression occurred. Twenty-eight patients had stage IV disease, and seven patients had stage IIIA or B disease. There was one complete and seven partial responses (overall response rate, 23%). Two of these responses were in patients with stage III disease (29%) and six in patients with stage IV disease (21%). Median survival was 8.7 months, and 36% of patients were alive at 1 year. There were no treatment-related deaths and little grade 3 or 4 non-haematological toxicity although grade 3 or 4 neutropenia occurred in 60% of patients (33% of cycles). There were four episodes of febrile neutropenia. The combination of paclitaxel and oral etoposide is active in advanced NSCLC and can be delivered with acceptable toxicity.

Administration, Oral↗
PubMed2000

Involvement of Shc and Cbl-PI 3-kinase in Lyn-dependent proliferative signaling pathways for G-CSF.

Granulocyte colony-stimulating factor (G-CSF) is the major hematopoietic factor which controls the production and differentiation of granulocytes. The G-CSF receptor (G-CSFR) belongs to the superfamily of the cytokine receptors, which transduce signals via the activation of cytosolic protein tyrosine kinases (PTK). To determine the role of specific PTK in G-CSF signaling we expressed the human G-CSFR in cell lines derived from DT40 B cells, which lack either the Src-related Lyn or Syk. Wild-type (wt) and syk-deficient cells underwent increased DNA synthesis in response to G-CSF; lyn-deficient cells did not. The purpose of these studies is to identify Lyn's downstream effectors in mediating DNA synthesis. While G-CSF stimulated Ras activity in all cell lines, G-CSF failed to induce the tyrosine phosphorylation of Shc in lyn-deficient cells. G-CSF induced a statistically significant activation of Erk1/Erk2 Kinase or p90Rsk only in the wt cells. G-CSF induced the tyrosine phosphorylation of Cbl and increased activity of PI 3-kinase in wild-type and syk-deficient, but non in lyn-deficient, cells. Inhibition of Shc by over-expression of its SH2 or PTB domains or PI 3-kinase by either treatment with wortmannin or expression of the CblY731F mutant decreased G-CSF-induced DNA synthesis. Thus, the Lyn, Cbl-PI 3-kinase, and Shc/non-Ras-dependent pathways correlate with the ability of cells to respond to G-CSF with increased DNA synthesis.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Promoting patient participation in the cancer consultation: evaluation of a prompt sheet and coaching in question-asking.

Active participation in the medical consultation has been demonstrated to benefit aspects of patients' subsequent psychological well-being. We investigated two interventions promoting patient question-asking behaviour. The first was a question prompt sheet provided before the consultation, which was endorsed and worked through by the clinician. The second was a face to face coaching session exploring the benefits of, and barriers to, question-asking, followed by coaching in question-asking behaviour employing rehearsal techniques. Sixty patients with heterogeneous cancers, seeing two medical oncologists for the first time, were randomly assigned to one of three groups: two intervention groups and one control group. Sociodemographic variables and anxiety were assessed prior to the intervention which preceded the consultation. The consultations were audiotaped and subsequently analysed for question-asking behaviour. Anxiety was assessed again immediately following the consultation. Questionnaires to assess patient satisfaction, anxiety and psychological adjustment were sent by mail 2 weeks following the consultation. Presentation and discussion of the prompt sheet significantly increased the total number of questions asked and the number of questions asked regarding tests and treatment. Coaching did not add significantly to the effects of the prompt sheet. Psychological outcomes were not different among the groups. We conclude that a question prompt sheet addressed by the doctor is a simple, inexpensive and effective means of promoting patient question asking in the cancer consultation.

Adaptation, Psychological↗
PubMed1998

The use of unproven methods of treatment by cancer patients. Frequency, expectations and cost.

The use of unproven therapies is of concern for a number of reasons, including the lack of scientific evidence of support them, their potential financial costs and the possibility of interference with conventional treatment. This study explored the prevalence, predictors and experiences of unproven therapy use by cancer patients attending an oncology clinic at an Australian teaching hospital. A questionnaire was administered to patients whilst they were waiting for a consultation with their oncologist. A total of 173 patients were invited to participate, and 156 consented to complete the survey (90%). Over half the patients (81, 52%) had used at least one unproven therapy since their diagnosis, and 28% had used three or more. Patients most commonly practised mediation/relaxation, changed their diet and used multi-vitamins. Most expected that the therapies would aid their conventional treatments and make them feel more in control of their situation. Benefits reported were largely psychological, such as an increased sense of control or a reduction in anxiety. Younger patients, those with early stage or advanced metastatic disease and those who had used unproven therapies prior to developing cancer were more likely to use unproven therapies. Health professionals involved in the care of cancer patients should be prepared to discuss the use of unproven therapies and try to identify and deal with unmet needs to help patients to cope with their illness.

Adult↗
PubMed1998

Non-surgical therapy for patients with advanced non-small cell lung cancer.

Non-small cell lung cancer is the major cancer problem in the Western World. Treatment and prognosis are highly stage dependent, although overall only 5-10% of patients will be alive 5 years after diagnosis. Patients with early stage disease are treated with surgery alone. However, for patients with locally advanced disease there is increasing evidence that combined modality approaches, incorporating chemotherapy, radiotherapy and/or surgery result in modest improvements in survival. For patients with metastatic non-small cell lung cancer there is evidence from metaanalyses and randomised studies that chemotherapy results in improvements in both duration and quality of life. Despite these advances, there is substantial room for further improvement and therefore, wherever possible, patients should be enrolled in well designed clinical studies.

Antineoplastic Agents↗
PubMed1998

New chemotherapeutic agents in the treatment of non-small cell lung cancer: the Australian experience.

The disappointing results obtained with currently available chemotherapy for lung cancer has led to the development of several new agents over the past 5 years. These include paclitaxel, docetaxel, vinorelbine, gemcitabine, and the camptothecins, irinotecan and topotecan. To date, phase I and II clinical trials with paclitaxel, docetaxel, gemcitabine, and combinations containing these drugs have been performed in patients with non-small cell lung cancer in Australia. These trials have produced overall response rates of 10 to 40%, which are similar to the rates obtained in other studies with these agents. In general, the agents have been well tolerated. However, these studies cannot be compared with previous studies employing conventional chemotherapeutic agents, primarily because the results of the former studies may have been skewed due to enrollment of younger, healthier patients and a variable proportion of patients with locally advanced rather than metastatic disease. Randomized controlled trials will be needed to determine whether use of these newer agents is associated with improvements in survival, palliation, and/or toxic reactions when compared with currently used regimens.

Antimetabolites, Antineoplastic↗
PubMed1997

Recent advances in managing non-small-cell lung cancer: 4. Chemotherapy of metastatic cancer.

Chemotherapy has been shown to prolong survival and to be cost effective in the palliative treatment of non-small-cell lung cancer. A meta-analysis of 11 randomised trials has found a small benefit from combination chemotherapy in advanced NSCLC, increasing one-year survival rates from 5% to 15%. New combination regimens, especially carboplatin-paclitaxel, show higher response rates in selected patients, and promise improved survival rates, but this has yet to be confirmed in randomised trials.

Antimetabolites, Antineoplastic↗
PubMed1997

Active surveillance after orchiectomy for nonseminomatous testicular germ cell tumors: late relapse may occur.

OBJECTIVES: To review the outcome of men with Stage I nonseminomatous germ cell tumors managed with a policy of active surveillance following orchiectomy. METHODS: The clinical records of all men with Stage I nonseminomatous germ cell tumors seen at Royal Prince Alfred Hospital, Australia between 1982 and 1995 were reviewed. Data were obtained concerning the histologic type of tumor, levels of serum tumor markers, relapse and subsequent treatment, and survival. RESULTS: Seventy-seven patients were entered into the active surveillance protocol between 1982 and 1995. With a minimum follow-up of 2 years, 27 (35%) have relapsed, with a median time to relapse of 5 months. Two late relapses occurred at 37 and 57 months after diagnosis. Relapses occurred most commonly in the retroperitoneal lymph nodes, with the lungs the second most common site. Following treatment with chemotherapy and surgery, all patients achieved complete remission, with 1 patient subsequently relapsing and ultimately dying of progressive tumor. One other patient died of acute myeloid leukemia, thought to be secondary to chemotherapy. Overall, 75 patients (97%) remain alive and free of disease. CONCLUSIONS: Active surveillance is a safe and effective approach to the management of Stage I nonseminomatous germ cell tumors. Although most relapses occur within the first 2 years, late relapses may occur.

Adolescent↗
PubMed1997

The dynamics of change: cancer patients' preferences for information, involvement and support.

BACKGROUND: While the importance of providing individualised communication to cancer patients is now well recognised, little is known about the stability and validity of patients' expressed preferences for information and involvement in decision-making. This study explored the stability and possible predictors of such preferences over time. PATIENTS AND METHODS: Cancer patients seeing two Medical Oncologists in an out-patient clinic at an Australian teaching hospital completed a questionnaire battery before and directly after one consultation, and before their next consultation. Eighty consecutive patients with heterogeneous cancers participated in the study. Preferences for general and specific information, involvement and support were elicited at each assessment. Locus of control and patient familiarity with the clinic were measured before the first consultation. Patient satisfaction with the consultation was assessed directly after the consultation. Demographic and disease data were recorded for each patient. RESULTS: General preferences for information and involvement were relatively stable, at least in the short term; however there was considerable variability in preferences for specific topics of information. Patients whose condition had recently worsened were more likely to want progressively less involvement in decision-making. Gender, the doctor seen and religion were also predictive of patient preferences. CONCLUSIONS: Situational factors, such as change in disease status, may alter a patient's preferences for information and involvement. If we wish to match the provision of information and support to the expressed needs of patients, we must ask patients at each consultation what those needs are.

Adolescent↗