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Biomedical subjects

A S Coates

Publications and source records attributed to A S Coates.

At least 19 recordsLinked to original sources
PubMed1995

Elective lymph node dissection in patients with primary melanoma of the trunk and limbs treated at the Sydney Melanoma unit from 1960 to 1991.

BACKGROUND: The value of elective lymph node dissection (ELND) in melanoma remains controversial. Published prospective and retrospective studies can be criticized, and results from two ongoing randomized trials are not yet available. A previous retrospective review from the Sydney Melanoma Unit (SMU) showed apparent survival benefit from ELND, especially in tumors of intermediate thickness. STUDY DESIGN: We undertook a retrospective analysis of all patients treated at the SMU since 1960 for melanoma of the trunk or limbs measuring 1.5 mm or more in thickness, without clinical lymph node metastases, whose definitive wide excision (WE) with or without ELND was performed at the SMU within 60 days of initial diagnosis. RESULTS: There were 1,278 patients who fulfilled these criteria. Of these, 845 (66 percent) were treated with ELND and the remaining 34 percent were treated with WE alone. The median follow-up period was 58 months. Patients with thicker tumors and younger age more commonly underwent ELND. Among patients with thinner tumors, males underwent ELND more commonly than females. A multivariate proportional hazard model of melanoma-specific survival stratified by tumor thickness was chosen to allow for the imbalances between the two groups. With or without allowance for covariates, no benefit from ELND was found in the whole group or any subset. In contrast to previous studies from the SMU, we deliberately excluded from the present study patients referred only after WE with or without ELND elsewhere, because these might have been a selectively biased poor prognostic group. CONCLUSIONS: This study does not indicate a benefit from ELND for melanomas of the trunk or limbs measuring over 1.5 mm in thickness.

Female↗
PubMed1994

Effect of systemic adjuvant treatment on first sites of breast cancer relapse.

Adjuvant systemic treatment for resectable breast cancer changes the natural history of the disease but provides only a small and delayed effect on survival. Evaluation of the types of first relapse avoided by available treatments may explain why effects on mortality are small and appear late during follow-up. In randomised clinical trials done by the International Breast Cancer Study Group (IBCSG) between 1978 and 1985, 2108 patients with node-positive disease received more-effective treatments (6 or more cycles of cyclophosphamide, methotrexate, fluorouracil and prednisone; with or without tamoxifen, or tamoxifen and prednisone alone), and 722 patients received less-effective treatments (no treatment or a single cycle of chemotherapy). 3 main categories of first site of relapse were defined and evaluated by cumulative incidence analysis: local or regional, and distant soft tissue, bone, and viscera. The more-effective treatments reduced the cumulative incidence of first relapse in local or regional and distant soft tissue sites at 10 years from 36% to 18% (p = 0.0001); first relapse in bone and viscera was not altered by the more-effective treatments. These results were similar for premenopausal and postmenopausal women, and for patients with oestrogen-receptor-positive or oestrogen-receptor-negative tumours. Adjuvant systemic treatments in current use improve patient outcome mainly by reducing the incidence of first local or regional and distant soft-tissue relapses, while first recurrences in bone or viscera are influenced much less. More intensive treatments at present being tested in clinical trials might affect bone and visceral relapses and have a greater and earlier influence on survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Long term response to chemotherapy in patients with visceral metastatic melanoma.

PATIENTS AND METHODS: Eight patients who remain in long term remission 4 to 15 years after chemotherapy for visceral metastatic melanoma are described. These patients were observed among some 1100 patients with visceral melanoma seen at the Sydney Melanoma Unit between 1977 and 1989. Only about one-third of such patients received chemotherapy, almost always with single agent dacarbazine or a nitrosourea. RESULTS: The apparently cured patients did not differ from the overall group of patients with visceral metastases in baseline characteristics, but 6 of the 8 had nodular lung metastases. CONCLUSIONS: While the mechanism remains uncertain, one possibility could be that chemotherapeutic agents cause mutations which allow expression of antigenicity in tumour cells. In any case, the fact of occasional exceptionally good responses, perhaps amounting to cure, constitutes an argument for a trial of chemotherapy in patients with visceral metastatic melanoma.

Adolescent↗
PubMed1992

Meta-analysis: the fashion of summing-up evidence. Part II: Interpretations and uses.

In this commentary, we use evidence produced by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) ten-year update of a meta-analysis of trials of adjuvant therapies for early breast cancer which started prior to 1985 to illustrate aspects of interpretations and uses of meta-analysis results. The following issues are discussed: i) The meta-analysis provides an average summary for the effect of a treatment. Greater statistical power is obtained by increasing the number of events contributing to the analysis. However, summing up the results of various trials necessitates the loss of individual information concerning the magnitude of treatment effects which depend on tumor- and patient-related factors. Subgroup analyses within the meta-analysis process allow some recovery of such features; ii) The absolute benefit obtained from an effective treatment depends not only on the relative benefit of the treatment but also on the prognosis of the individual patients; iii) The results are more immediately applicable if less reliance is placed on the arithmetic construct inherent in the overview, using instead unconfounded information about the value of treatments actually administered. This avoids the need to extrapolate the effect for one component of the therapy by assuming a lack of interaction with its other components; iv) Although indirect comparisons between different meta-analyses are regularly made to pick the "winner" from among tested treatment modalities, it is unlikely that the optimal therapeutic regimen can be defined via such indirect comparisons, though such comparisons may raise interesting, testable hypotheses.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Severe vascular adverse effects with thrombocytopenia and renal failure following emetogenic chemotherapy and ondansetron.

During late 1991, a series of severe adverse events involving thrombocytopenia, renal insufficiency and thrombotic episodes was observed in patients receiving emetogenic chemotherapy. Two patients died, one of renal failure and one of cerebral haemorrhage in the presence of thrombocytopenia. Other severe side effects included thrombosis of the aorta causing paraplegia and multifocal cerebral infarctions. Common exposure features included the use of ondansetron and dexamethasone as antiemetics, and in most of the cases high dose (100 mg/M2 or more) cisplatin. Retrospective review of a series of patients treated with similar cytotoxic regimens for similar diseases before the use of ondansetron revealed no similar adverse effects, but no substantial differences were observed in renal function or haematologic toxicity in the two groups overall. Sporadic adverse vascular events have been observed before the use of ondansetron. The mechanism remains unknown, and it is not clear whether ondansetron was a factor in the unusual incidence of such events in the present series.

Adult↗
PubMed1991

Experience with 998 cutaneous melanomas of the head and neck over 30 years.

Between 1960 and 1990, a total of 998 patients were treated at the Sydney Melanoma Unit for cutaneous melanoma of the head and neck. There were 595 male and 403 female patients, with a median age of 53 years. The most common primary lesion site was the face (47%), followed by the neck (29%), scalp (14%), and ear (10%). Histologic types were as follows: superficial spreading 30%, nodular melanoma 28%, lentigo maligna melanoma 16%, and other 26%. All patients underwent surgical treatment. Primary closure of wounds was achieved in 52% of patients, and excision margins were 2 cm or less in 45%. A total of 152 patients had therapeutic neck dissections, and 234 had elective neck dissections. The overall local recurrence rate was 13%, and this was significantly influenced by increasing tumor thickness and Clark level. The recurrence rate in the neck after neck dissection was 24%, and the rate of parotid recurrences was 14%. Melanoma-specific survival was 77% at 5 years and 66% at 10 years for the entire group. By univariate analysis, survival varied significantly with age, tumor thickness, ulceration, anatomic sub-site, histologically positive nodes, and the presence of distant metastases. A diagnosis of lentigo maligna melanoma and elective lymph node dissection both appeared to improve survival. With multivariate analysis, all of these factors remained significant prognostic factors except elective node dissection, which lost its beneficial influence.

Female↗
PubMed1991

Synchronous cisplatin infusion during radiotherapy for the treatment of metastatic melanoma.

In two pilot studies, 55 patients with symptomatic metastases from malignant melanoma were treated with irradiation and concurrent cisplatin. In the first group, cisplatin was given as a continuous intravenous infusion of 20 mg/m2 per day on days 1-5 and 22-26, with irradiation on days 2, 5, 9, 16, 23 and 26. The second group received 20 mg cisplatin over 24 h commencing 1 h before each fraction of irradiation on days 1, 4, 8, 11, 15 and 18. The first series of 28 patients had 30 lesions treated. Nine (30%) of these lesions responded completely and 10 (33%) achieved partial response for an overall response rate of 63% (95% confidence interval 44-80%). Survival was not evaluated in this group. The second group was comprised of 27 patients, with one irradiated lesion each. 1 patient achieved a complete response and 13 (48%) a partial response for an overall response rate of 52% (32-71%). Median survival was 21 weeks (16-31 weeks). Treatment was well tolerated with nausea and vomiting being the most common toxicity. Synchronous cisplatin infusion with radiotherapy achieves high response rates in metastatic melanoma. Whether it is superior to radiotherapy alone will require evaluation in a randomised trial.

Adult↗
PubMed1991

Retrospective review of chemotherapy for small cell lung cancer in the elderly: does the end justify the means?

Between 1978 and 1983, 72 patients aged 70 years or older (median 72, range 70-80) were treated for biopsy-proven, small cell lung cancer (SCLC). Intercurrent disorders were common, including ischaemic heart disease, peripheral vascular disease, chronic airflow limitation and second malignancies. 26 patients (36%) had limited extent of disease, and 46 (64%) had extensive disease. "Intensive" chemotherapy incorporating vincristine, cyclophosphamide and doxorubicin (OCA regimen) was administered to 32 patients [complete response (CR) + partial response (PR) = 84%]; less rigorous regimens (e.g. single agent chemotherapy, planned dose reductions, radiotherapy only) were used in 34 cases (CR + PR = 52%); and 6 received no active treatment. In the intensively treated group, there were 3 treatment-related deaths and 26 episodes of WHO grade 3-4 toxicity. In the less intensively treated group, there were no treatment-induced deaths and only 1 episode of severe toxicity. The overall median survival was 25 weeks (36 weeks for intensive treatment, 16 weeks with less intense treatment). For patients with limited disease only, the median survival in each group was 43 and 26 weeks, respectively. Intensive treatment for elderly patients with small cell lung cancer is associated with substantially increased toxicity and higher response rates than for gentle treatment, but without a major survival benefit.

Age Factors↗
PubMed1989

Changing character of cervical cancer in young women.

To examine the hypothesis that the pattern of cervical cancer is changing data on women presenting with the disease over 34 years were studied retrospectively. During 1953-86, 2628 women with cervical cancer were referred to a large tertiary referral hospital in Sydney; 418 were aged 35 or less. During the period of review the proportion of young women with the disease increased from under 9% in the 1950s and 1960s to about 25% in the 1970s and 1980s; a similar but less pronounced trend was apparent for the whole of New South Wales in the 1970s and 1980s. The prevalence of less common morphological types of cervical cancer increased throughout the period, particularly in the young. Pelvic lymph node metastases were identified in younger patients with stage Ib and IIa tumours more commonly in the later years of the study, suggesting that the disease was becoming more severe. Overall rates of recurrence improved over time, but an apparent increase in early recurrences was observed in young patients with Ib and IIa tumours and without nodal disease. The results suggest that the clinical and pathological behaviour of cervical cancer changed over the period of review.

Adult↗
PubMed1989

Costs and benefits of adjuvant therapy in breast cancer: a quality-adjusted survival analysis.

The use of adjuvant chemotherapy for postmenopausal patients with early breast cancer remains controversial because the potential benefits in terms of prolongation of disease-free survival (DFS) and overall survival (OS) must be balanced against the toxicity of treatment. Following mastectomy, 463 evaluable postmenopausal women with node-positive breast cancer were randomized to receive either chemoendocrine therapy for 1 year, or endocrine therapy alone for 1 year, or no adjuvant therapy (Ludwig Trial III). At 7-years median follow-up, OS was longer for the chemoendocrine-treated patients compared with controls (P = .04) and compared with the adjuvant endocrine therapy-alone group (P = .08). In order to balance this therapeutic advantage against the toxic effects of treatment, OS time was divided into time with toxicity (TOX), time without symptoms and toxicity (TWiST), and time after systemic relapse (REL). TOX and REL were weighted by coefficients of utility relative to TWiST and the results added to give a period of quality-adjusted survival (Q-TWiST). Benefits measured by Q-TWiST generally favored chemoendocrine therapy. For example, if TOX and REL were both given utility coefficients of 0.5 relative to 1.0 for TWiST, then by 7 years the average Q-TWiST for chemoendocrine therapy was 6.7 months longer than for no-adjuvant therapy (P = .05) and 4.1 months longer than for endocrine therapy alone (P = .20). Quality-adjusted survival analysis is recommended in assessing costs and benefits of toxic adjuvant therapy. In this example, it supports the use of chemoendocrine therapy in postmenopausal node-positive patients for a wide range of relative values assigned to periods with symptoms and toxicity.

Antineoplastic Agents↗
PubMed1988

Chemotherapy of advanced head and neck cancer: updated results of a randomized trial of the order of administration of sequential methotrexate and 5-fluorouracil.

One hundred and twenty-seven patients with advanced or recurrent squamous cell carcinoma of the head and neck (HNC) were randomized to treatment with methotrexate (MTX) followed 1 hour later by 5-fluorouracil (5-FU) (sequence MF), or 5-fluorouracil followed after 1 hour by methotrexate (sequence FM). One hundred and seventeen patients were evaluable for response. There was no significant difference in response rates between the MF and FM sequences. Overall, 8 patients (6.8%) achieved complete response (CR) and 46 (39.3%) partial response (PR). In 95 previously untreated patients, the overall response rate (CR + PR) was 50%, compared with 31% for previously treated patients (P = 0.02). Survival duration significantly favored the FM sequence in univariate analyses (P = 0.04). Stepwise multivariate Cox model analysis showed that poor performance status (Eastern Cooperative Oncology Group) at study entry (P less than 0.001) and prior radiotherapy (P = 0.03) were significant adverse predictors for survival. When allowance was made for these factors, a survival difference in favor of the FM sequence remained (P = 0.003). Sequential MTX followed 1 hour later by 5-FU is not recommended for treatment of HNC.

Antineoplastic Combined Chemotherapy Protocols↗