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Biomedical subjects

R Stuart-Harris

Publications and source records attributed to R Stuart-Harris.

At least 19 recordsLinked to original sources
PubMed2006

Phase II trial of weekly docetaxel for patients with relapsed ovarian cancer who have previously received paclitaxel--ANZGOG 02-01.

OBJECTIVE: To determine the response rate of weekly docetaxel in women with relapsed epithelial ovarian cancer previously treated with paclitaxel and at least one line of platinum-based chemotherapy. METHODS: In this multi-center phase II trial, 37 patients with relapsed disease were enrolled and treated with weekly docetaxel at 35 mg/m for 5 out of 6 consecutive weeks. Two patient cohorts were considered, those who progressed or relapsed within 4 months (N=7) or at greater than 4 months (N=30) from the time of completing their last course of paclitaxel. RESULTS: Patients in both cohorts received a median of 2 cycles of treatment (range; 1-4). In evaluable patients, the combined overall response rate, using both CA125 and RECIST response criteria was 18.9% (7/37; 95% CI; 10-34%). The combined overall progression-free survival was 3.1 months (95% CI; 2.5-3.8), and the combined overall survival was 12.3 months (95% CI; 8.2-16.4). Treatment was generally well tolerated with the only grade 4 toxicity being skin toxicity (3%). The most common grade 3 toxicities were fatigue (14%) and watery eyes (8%) with grade 3 neutropenia observed in only 5% of patients. CONCLUSION: Weekly docetaxel is well tolerated and has activity in patients with relapsed ovarian cancer previously treated with platinum and paclitaxel.

Antineoplastic Agents↗
PubMed2001

Isolated central nervous system relapse of non-seminomatous germ cell tumour of the testis. A case report and review of the literature.

Isolated central nervous system (CNS) relapse of non-seminomatous germ cell tumour (NSGCT) of the testis has been reported in only 12 patients previously. We report a patient with an isolated CNS relapse of NSGCT, following a prior systemic relapse. From a review of previous cases, isolated CNS relapse appears to be more common in patients with embryonal cell histology (alone or mixed with other elements) and occurred after a median of 8.5 months following initial presentation. Long-term survival appears possible using multi-modal treatment with whole-brain radiotherapy, surgery and/or chemotherapy. However, the optimal treatment of isolated CNS relapse remains undefined.

Adult↗
PubMed2000

The pharmacokinetics of morphine and morphine glucuronide metabolites after subcutaneous bolus injection and subcutaneous infusion of morphine.

AIMS: To investigate the pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) in healthy volunteers after the administration of morphine by subcutaneous bolus injection (s.c.b.) and subcutaneous infusion (s.c. i.) over 4 h, and to compare the results with the intravenous bolus (i.v.) administration of morphine. METHODS: Six healthy volunteers each received 5 mg morphine sulphate by i.v., s.c.b. and short s.c.i. over 4 h, on three separate occasions, in random order, each separated by at least 1 week. Plasma samples were assayed for morphine, M6G and M3G. RESULTS: After i.v. morphine, the concentrations of morphine, M6G and M3G and their pharmacokinetic parameters were similar to those we have observed previously, in other healthy volunteers (when standardized to nmol l- 1, for a 10 mg dose to a 70 kg subject). After s.c.b. morphine, similar results were obtained except that the median tmax values for morphine and M3G were significantly longer than after i.v. morphine (P< 0.001 and P< 0.05, respectively), with a trend to a longer tmax for M6G (P = 0. 09). The appearance half-lives after s.c.b. morphine for M6G and M3G were also significantly longer than after i.v. morphine (P = 0.03 and P< 0.05, respectively). Comparison of log-transformed AUC values indicated that i.v. and s.c.b. administration of morphine were bioequivalent with respect to morphine, M6G and M3G. In comparison with i.v. morphine, morphine by s.c.i. was associated with significantly longer median tmax values for morphine (P< 0.001), M6G (P< 0.001) and M3G (P< 0.05), and the mean standardized Cmax values significantly lower than after both i.v. and s.c.b. morphine (morphine P< 0.001, M6G P< 0.001 and M3G P< 0.01 for each comparison). Comparison of log-transformed AUC values after i.v. and s.c.i. morphine indicated that the two routes were not bioequivalent for morphine (log-transformed AUC ratio 0.78, 90% CI 0.66-0.93), M6G (0.72, 90% CI 0.63-0.82), or M3G (0.65, 90% CI 0.54-0.78). A small stability study indicated no evidence of adsorptive losses from morphine infused over 4 h using the infusion devices from the study. CONCLUSIONS: Although bioequivalence was demonstrated between the s. c.b. and i.v. routes of morphine administration, the bioavailabilities of morphine, M6G and M3G after s.c.i. were significantly lower than after i.v. administration. However, despite this, the study demonstrates that the subcutaneous route is an effective method for the parenteral administration of morphine.

Adult↗
PubMed1995

The Sacred Heart Hospice: an Australian centre for palliative medicine.

The Sacred Heart Hospice, Sydney, was founded in 1890 and is the largest inpatient palliative-care facility in Australia. Patients with advanced cancer form the predominant patient group, although patients with HIV/AIDS account for approximately 20% of admissions. A community-outreach service, established in 1983, cares for more patients at home than in the Hospice. Recently the Hospice has participated in a number of clinical trials and intends to become a regional centre for palliative-care research, education and training.

Allied Health Personnel↗
PubMed1995

Continuous infusion of vincristine, ifosfamide and epirubicin over 6 weeks in treatment-resistant advanced breast cancer.

28 patients with recurrent advanced breast cancer were treated with a salvage regimen consisting of vincristine, epirubicin and ifosfamide/mesna (VIE). All patients had poor prognostic characteristics defined as relapse within 12 months of chemotherapy or as relapse within a radiotherapy field. Chemotherapy was infused continuously through a central venous catheter using a portable pump. Ifosfamide (3 g/m2) mixed with mesna (3 g/m2) was infused for 7 days followed by epirubicin (50 mg/m2) mixed with vincristine (1.5 mg/m2) over a further seven days and alternated for a total of 6 weeks. 9 of the 28 patients (32%) responded to VIE (six partial and three complete responses). This included 6 of the 18 patients (33%) who had previously received doxorubicin or mitoxantrone, 6 of the 17 patients (35%) who had an inoperable in-field relapse after radiotherapy for locally advanced cancer, and 5 of the 21 patients (24%) relapsing within 6 months of previous chemotherapy. Median duration of response and overall survival were 3.7 and 6.9 months, respectively. Myelotoxicity was mild. One patient had neutropenic sepsis, 3 patients ahd grade 3 nausea and vomiting and one patient developed paralytic ileus attributed to vincristine. Central venous catheter complications occurred in 12 of 33 catheters requiring removal in 6. Continuous infusional chemotherapy using vincristine, epirubicin and ifosfamide achieves a 32% overall response rate in treatment-resistant advanced breast cancer, and is associated with minimal toxicity and a short treatment period. VIE may be a suitable alternative to conventional chemotherapy.

Adult↗
PubMed1994

Filgrastim in patients with chemotherapy-induced febrile neutropenia. A double-blind, placebo-controlled trial.

OBJECTIVE: To determine if filgrastim (recombinant human methionyl granulocyte colony-stimulating factor) used in addition to standard inpatient antibiotic therapy accelerated recovery from infection associated with chemotherapy-induced neutropenia. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Hematology and oncology wards of four teaching hospitals. PATIENTS: 218 patients with cancer who had fever (temperature > 38.2 degrees C) and neutropenia (neutrophil count < 1.0 x 10(9)/L) after chemotherapy. INTERVENTION: Patients were randomly assigned to receive filgrastim (12 micrograms/kg of body weight per day) (n = 109) or placebo (n = 107) beginning within 12 hours of empiric therapy with tobramycin and piperacillin. Patients received treatment and remained in the study until the neutrophil count was greater than 0.5 x 10(9)/L and until 4 days without fever (temperature < 37.5 degrees C) had elapsed. MEASUREMENTS: Days of neutropenia and fever and days in the study (hospitalization); time to resolution of fever and febrile neutropenia; and frequency of the use of alternative antibiotics. RESULTS: Compared with placebo, filgrastim reduced the median number of days of neutropenia (3.0 compared with 4.0 days of a neutrophil count of < 0.5 x 10(9)/L; P = 0.005) and the time to resolution of febrile neutropenia (5.0 compared with 6.0 days; P = 0.01) but not days of fever (3.0 days for both groups). The frequency of the use of alternative antibiotics was similar in the two groups (46% compared with 41%; P = 0.48). The median number of days patients were hospitalized while on study was the same (8.0 days; P = 0.09); however, filgrastim decreased the risk for prolonged hospitalization (> 11 days, 4th quartile) by half (relative risk, 2.1 [95% CI, 1.1 to 4.1]; P = 0.02). In exploratory subset analyses, filgrastim appeared to provide the greatest benefit in patients with documented infection and in patients presenting with neutrophil counts of less than 0.1 x 10(9)/L. CONCLUSIONS: Filgrastim treatment used with antibiotics at the onset of febrile neutropenia in patients with cancer who have received chemotherapy accelerated neutrophil recovery and shortened the duration of febrile neutropenia.

Adolescent↗
PubMed1994

A phase II study of carboplatin and cisplatin in advanced ovarian cancer.

In view of the single agent activity of both cisplatin and carboplatin in epithelial ovarian cancer, and their different toxicity profiles, we carried out a phase II study of low dose cisplatin (50 mg/m2) in combination with moderate dose carboplatin (300 mg/m2) in patients with advanced ovarian cancer. Fourteen patients, all of whom had bulky disease and over half of whom had Stage IV disease, were eligible for assessment of response and toxicity. An overall response rate of 71% was demonstrated (57% complete response, 14% partial response), which is at least equivalent to other regimens used in first line treatment of ovarian cancer. Toxicities encountered were nausea/vomiting and myelosuppression, however no serious renal neuro or ototoxicity was observed and the regimen does not cause significant alopecia. This combination may be a practical alternative to regimens which use high dose cisplatin to achieve similar efficacy.

Aged↗
PubMed1993

Hypercalcaemia in small cell lung cancer: report of a case associated with parathyroid hormone-related protein (PTHrP).

Although hypercalcaemia is frequently associated with malignancy, it is very rare in small cell lung cancer despite the high incidence of lytic bone metastases. We report a patient with extensive small cell cancer who presented with hypercalcaemia. Investigations suggested parathyroid hormone (PTH) receptor stimulation, although the serum PTH level was not elevated. PTH related protein (PTHrP) was localised in a biopsy specimen from the tumour. Although hypercalcaemia is rare in small cell lung cancer, when hypercalcaemia does occur, PTHrP may be a causal factor.

Aged↗
PubMed1993

The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian Germ Cell Trial Group.

PURPOSE: In an effort to maintain the excellent long-term results achieved with combination chemotherapy for good-prognosis germ cell carcinoma, but to reduce the toxicities encountered, a randomized trial was conducted comparing cisplatin and vinblastine with or without bleomycin. PATIENTS AND METHODS: Two hundred eighteen assessable patients with a good prognosis were randomized to receive induction chemotherapy with cisplatin 100 mg/m2 intravenously (IV) day 1 and vinblastine 6 mg/m2 IV days 1 and 2 every 3 weeks (PV) with or without bleomycin 30 mg intramuscularly (IM) weekly (PVB) for a maximum of 12 weeks. Once maximum response was achieved, patients with a complete remission (CR) received two courses of consolidation chemotherapy, while those with residual abnormalities and normal tumor markers underwent surgical resection whenever possible. RESULTS: Toxicities encountered in this study were clearly greater for those patients who received bleomycin, with significantly more leukopenia, thrombocytopenia, anemia, alopecia, and renal and pulmonary toxicities. The proportion of patients who achieved CR and had no evidence of disease (resection of all viable malignancy) was 89% for PV and 94% for PVB (P = .29). After a minimum of 4 years of follow-up, relapses have occurred in 7% of patients who received PV and 5% who received PVB. A total of five patients on each therapy arm were successfully treated with further salvage chemotherapy and surgery. Thus, deaths from progressive malignancy have occurred in 15% of patients on PV and 5% on PVB (P = .02), a rate that was partly offset by the higher proportion of toxic deaths with PVB (P = .06). CONCLUSION: Despite the toxicities encountered with bleomycin in cisplatin-based combination chemotherapy for these patients, complete deletion of this drug compromises therapeutic efficacy.

Adolescent↗
PubMed1993

Ifosfamide combination regimens for soft-tissue sarcoma.

Two trials using ifosfamide-based combination chemotherapy for advanced soft-tissue sarcoma have been completed. In the first study, 50 evaluable patients received ifosfamide (5 g/m2) with mesna (5 g/m2) and doxorubicin (40 or 60 mg/m2) intravenously (i.v.) every 3 weeks. In all, 11 patients (22%) achieved an objective response [3 complete responses (CRs) and 8 partial responses (PRs)]. Toxicities included leukopenia, febrile neutropenia, nausea and vomiting, and alopecia. The overall median survival was 12 months. In the second study, 51 evaluable patients received ifosfamide (3 g/m2) with mesna (3 g/m2), both being given i.v. on day 1, together with etoposide (100 mg/m2) infused i.v. daily for 3 days. Six patients (12%) achieved objective responses (1 CR, 5 PRs). Toxicities included leukopenia, nausea and vomiting, and alopecia. The overall median survival was 7.4 months. Neither of these combination regimens appears to be more effective in advanced soft-tissue sarcoma than single-agent therapy with either ifosfamide or doxorubicin. If the results of chemotherapy in the management of these tumors are to be improved a new approach to therapy is clearly required.

Adolescent↗
PubMed1992

A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

PURPOSE: A prospective randomized trial was performed to determine if the addition of methotrexate, vinblastine, and doxorubicin to cisplatin (M-VAC) imparted a response rate or a survival advantage over single-agent cisplatin in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: From October 1984 through May 1989, 269 patients with advanced urothelial carcinoma were entered onto this international intergroup trial and randomized to receive intravenous (IV) cisplatin (70 mg/m2) alone or with methotrexate (30 mg/m2 on days 1, 15, 22), vinblastine (3 mg/m2 on days 2, 15, 22) plus doxorubicin (30 mg/m2 on day 2). Cycles were repeated every 28 days until tumor progression or a maximum of six cycles. There were 246 fully assessable patients of whom 126 were randomized to cisplatin alone and 120 were randomized to the M-VAC regimen. RESULTS: As expected, the M-VAC regimen was associated with a greater toxicity, especially leukopenia, mucositis, granulocytopenic fever, and drug-related mortality. Response rates were superior for the M-VAC regimen compared with single-agent cisplatin (39% v 12%; P less than .0001). Similarly, the progression-free survival (10.0 v 4.3 months) and overall survival (12.5 v 8.2 months) were significantly greater for the combined therapy arm. CONCLUSION: Although a more toxic regimen, we found M-VAC to be superior to single-agent cisplatin with respect to response rate, duration of remission, and overall survival in patients with advanced urothelial carcinoma.

Adult↗
PubMed1992

Carboplatin-containing regimens for small cell lung cancer: implications for management in the elderly.

The efficacy and toxicity of two regimens based on etoposide/carboplatin with or without cyclophosphamide/vincristine in the management of small cell lung cancer (SCLC) were assessed by the Australian Lung Cancer Study Group. Response rates of 77% and 85% were noted for the two- and four-drug regimens, respectively, among patients with limited disease (LD). Response rates among patients with extensive disease (ED) were 58% and 79%, respectively. The profiles of nonhematologic toxicity were modest; myelosuppression was dose-limiting when colony-stimulating factors were not used. Twenty-six patients (14%) were older than 70 years of age. Although hematologic toxicity was more severe in the elderly group, there was no significant difference in nonhematologic toxicity, response rate, or overall survival between the geriatric and younger groups. When LD only was considered, 33% of those younger than 70 were alive at 2 years; no patients aged 70 years or older with LD were alive beyond 2 years. In patients with ED, there was no age-related difference in survival. Cytotoxic regimens based on etoposide/carboplatin constitute useful treatment for SCLC, with high response rates and manageable toxicity, irrespective of patient age.

Adult↗
PubMed1991

Epirubicin: a phase II study in recurrent small-cell lung cancer.

Epirubicin (4'-epidoxorubicin), an analogue of doxorubicin (Adriamycin), has established activity in the treatment of small-cell lung cancer (SCLC) when used at doses of 75 to 120 mg/m2 in previously untreated patients. We completed a phase II study of epirubicin (85 mg/m2 given intravenously at 3-week intervals) in 20 patients with recurrent SCLC, all of whom had received prior combination chemotherapy. Of 19 patients who were assessable for response, 2 achieved a complete response and 2 a partial response, for an overall response rate of 4/19 (21%); 95% confidence interval, 8%-43%). Myelosuppression and alopecia were the most frequent toxicities; epirubicin was otherwise well tolerated, with other toxicities such as nausea and vomiting being infrequent or mild. Epirubicin at a dose of 85 mg/m2 exhibits modest single-agent activity in previously treated SCLC and is generally well tolerated. Given as a single agent or in combination with other well-tolerated drugs, epirubicin would be suitable in cases in which palliation of symptoms without undue toxicity is required in the management of previously treated SCLC.

Aged↗
PubMed1990

Etoposide, carboplatin, cyclophosphamide and vincristine in previously untreated patients with small-cell lung cancer.

The efficacy and toxicity of 120 mg/m2 etoposide and 100 mg/m2 carboplatin given i.v. daily x 3 together with 750 mg/m2 cyclophosphamide and 1.4 mg/m2 vincristine given i.v. on day 1 (ECCO) in a regimen given every 28 days for 6 courses was assessed in 90 (40 limited stage, 50 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to limited-stage patients without progression after 3 courses of chemotherapy. Cranial irradiation with 30 Gy in 10 fractions was given to all patients attaining a complete response (CR). Objective responses were seen in 83% [CR, 60%; partial response (PR), 23%] of patients with limited and 76% (CR, 22%; PR, 54%) of those with extensive disease. The median relapse-free survival for objective responders with limited disease was 13.4 months, with a median of 8.0 months for extensive-stage patients. The median relapse-free survival for patients achieving a CR was 13.4 months, with a median of 7.8 months for those undergoing a PR. The median survival was 13.3 months for patients with limited disease, with a median of 9.6 months for those with extensive disease. The median survival following a CR was 18.2 months, with a median survival of 9.9 months for those showing a PR. The combination was well tolerated, with either no nausea or nausea only (WHO grade 0 or 1) in 56% of patients and minimal mucositis, renal toxicity, neurotoxicity or ototoxicity. Neutropenia measuring less than 1.0 x 10(9) WBC/l (WHO grade 3 or 4) was seen in 74% of patients, with two deaths due to infection occurring during neutropenia. Thrombocytopenia of less than 50 x 10(9) platelets/l (WHO grade 3 or 4) occurred in 24% of patients. ECCO is a new, active, well-tolerated program for previously untreated patients with small-cell lung cancer.

Adult↗
PubMed1990

Identifying priorities of psychosocial need in cancer patients.

Inconsistent findings on the efficacy of psychosocial interventions in cancer may be due to their lack of specificity. The aim of this study was to identify priorities of psychosocial need among cancer patients currently receiving treatment in Western Sydney (NSW) as a prelude to targeted intervention. A sample of 188 patients (129 female, median age 52 years, median time since diagnosis 12 months), with various solid tumours, completed a self-report ranking questionnaire listing eight major areas of psychosocial need based on a literature search of relevant studies. The resulting ranking of priorities was: family (1), dealing with emotional stress (2), getting information (3), money (4), work (5), social life (6), sex life (7), and dealing with hospital staff (8). These priorities were independent of demographic characteristics, including time since diagnosis, suggesting that support in the areas of major need may be just as important during follow-up as it is at diagnosis. Males reported less distress than females, and patients with cancer of the head/neck or breast reported most distress. To be maximally effective, psychosocial intervention for cancer patients should focus on the principal areas of family interaction, effective stress management, and access to information.

Adult↗