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P J Hoskins

Publications and source records attributed to P J Hoskins.

At least 19 recordsLinked to original sources
PubMed2005

Carboplatin and paclitaxel for advanced and recurrent cervical carcinoma: the British Columbia Cancer Agency experience.

BACKGROUND: One of the most active chemotherapy combinations in advanced or recurrent cervical cancer is cisplatin-paclitaxel. However, this palliative regimen is associated with significant toxicity. Carboplatin-paclitaxel is thus an attractive option. METHODS: Patients with advanced or recurrent carcinoma of the cervix treated with carboplatin-paclitaxel from April 2000 were included in the study. Starting doses of carboplatin-paclitaxel were: AUC 5-6 and 155-175 mg/m(2), respectively, repeated every 28 days. RESULTS: Twenty-five women treated with this combination were identified. Twenty-three women (92%) had prior treatment with pelvic radiotherapy and 14 (56%) had had concurrent radio-sensitizing cisplatin. There was a 20% PR and a 20% CR rate (10/25). The median progression-free survival for the entire group was 3 months. Responders had a median PFS of 16 months. Fourteen patients (56%) had died of disease progression. The median overall survival (OS) was 21 months. Common toxicities included: grade 1 or 2 anemia, 68%; grade 3 or 4 anemia, 32%; grade 3 or 4 neutropenia, 32%; and grade 1 or 2 peripheral neuropathy, 24%. ECOG PS did not change significantly while on treatment. Eighty-four percent of treatments were delivered on time, and 96% at full dose. CONCLUSIONS: Carboplatin-paclitaxel is an active combination in advanced and recurrent cervical cancer. In this predominantly pre-irradiated group, the combination was deliverable, well tolerated, and the most commonly observed toxicity was anemia.

Adult↗
PubMed2003

Small-cell carcinoma of the cervix: fourteen years of experience at a single institution using a combined-modality regimen of involved-field irradiation and platinum-based combination chemotherapy.

PURPOSE: To determine the efficacy and toxicity of a combined-modality regimen of irradiation with platinum-based combination chemotherapy in small-cell carcinoma of the cervix (SCCC). PATIENTS AND METHODS: Thirty-four patients with SCCC were seen and treated at the British Columbia Cancer Agency between May 1988 and November 2002. Two protocols were used, SMCC (May 1988 to December 1995) and SMCC2 (January 1996 to November 2002). Both protocols used cisplatin, etoposide, and involved-field irradiation (essentially pelvis plus or minus para-aortics) with concurrent chemotherapy. In addition, SMCC2 included carboplatin and paclitaxel, and the para-aortics were irradiated routinely. RESULTS: Thirty-one patients received either SMCC (n = 17) or SMCC2 (n = 14), and three patients did not (disease too extensive, n = 1; patient refusal, n = 1; and alternative regimen, n = 1). For the 31 patients treated on one of the protocols, the 3-year overall and failure-free survival (FFS) rates were 60% and 57%, respectively. The results were equivalent for SMCC and SMCC2. Radiologic stage was the only independent predictor for FFS (80% at 3 years for stage I and II patients v 38% at 3 years for stage III and IV patients). Distant failure (28%) was the most common cause of failure, with local failure occurring in 13% of patients. The switch to SMCC2 did not improve efficacy but did lessen the toxicity. CONCLUSION: SCCC can be successfully treated in approximately 55% of patients with a combination of irradiation and platinum-based chemotherapy. Disease extent predicts for chance of curability.

Adult↗
PubMed2001

Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study.

PURPOSE: To evaluate the efficacy of carboplatin plus paclitaxel in primarily advanced or recurrent endometrial cancers. PATIENTS AND METHODS: Four distinct patient groups received carboplatin (area under the curve, 5 to 7) plus paclitaxel 175 mg/m(2) for 3 hours at 4-week intervals: group 1 (n = 21), patients with primarily advanced, nonpapillary serous cancers; group 2 (n = 20), the same as group 1 but with papillary serous cancers; group 3 (n = 18), recurrent, nonpapillary serous cancers; and group 4 (n = 4), recurrent, papillary serous cancers. Involved-field irradiation was used in groups 1 and 2 for those with radioencompassable disease. RESULTS: Sixty-three patients were treated. Response rates to chemotherapy in the assessable patients in the four groups were 78% (95% confidence interval [CI], 51% to 100%); 60% (95% CI, 35% to 85%), 56% (95% CI, 34% to 78%), and 50%, respectively. Nineteen patients (90%) in group 1 also were irradiated, and the median failure-free survival time for all 21 patients was 23 months, with a 62% 3-year overall survival rate. Eleven patients (55%) in group 2 were irradiated, and the median failure-free survival time for all 18 patients was 18 months, with a 39% 3-year overall survival rate. The median failure-free interval in the patients in group 3 was 6 months, with a 15-month median overall survival time. Toxicity was manageable, reversible, and predominantly hematologic. Two patients developed neutropenic fever, and three patients, including these two, were hospitalized for complications. CONCLUSION: Carboplatin-paclitaxel is an efficacious, low-toxicity regimen for managing primarily advanced or recurrent endometrial cancers.

Adult↗
PubMed1997

Cisplatin/etoposide chemotherapy for recurrent or primarily advanced cervical carcinoma.

Thirty-eight women with primarily advanced (n = 10) or recurrent (n = 28) cervical carcinoma were treated with cisplatin (30 mg/m2/day intravenously) and etoposide (60 mg/m2/day intravenously) for 3 days followed by oral etoposide, 50 mg daily for 7 days, repeated at 28-day intervals. The response rate was 39% (95% confidence limits 24-55%) with response duration of 5 to 36 months. The main toxicities were neutropenia (21% developing neutropenic fever), alopecia, stomatitis, and nausea and vomiting. Despite this all responders had maintained or improved quality of life as defined by symptoms and performance status.

Adult↗
PubMed1997

Advanced diffuse large-cell lymphoma treated with 12-week combination chemotherapy: natural history of relapse after initial complete response and prognostic variables defining outcome after relapse.

PURPOSE: To define both the natural history of and prognostic factors affecting outcome post relapse from a complete response in advanced stage diffuse large-cell lymphoma. PATIENTS AND METHODS: A total of 468 patients aged 17-74 years received the 12-week duration chemotherapy regimens MACOP-B, VACOP-B and ACOP-12 between 1 April 1981 and 31 December 1995 for advanced stage diffuse large, mixed or immunoblastic lymphoma. Of these 402 entered a complete remission, 97 (24%) of whom subsequently relapsed. Initial staging data, follow-up, and relapse information were analyzed to define the natural history of relapse and also subjected to univariate and multivariate correlation with overall (OS) and failure free survival (FFS). RESULTS: Eleven percent of the relapses were low grade. All other relapses were of intermediate grade with 75% occurring within the first two years, the remainder up until the eleventh year. Median and five-year OS from the time of relapse for intermediate grade relapse were 12 months and 20%; for FFS they were eight months and 18% respectively. Adverse independent factors, for both OS and FFS were: less than one year to relapse, decreasing performance status at relapse, and more than three nodal sites at relapse. CONCLUSIONS: Low-grade relapse is not uncommon in patients who initially presented with diffuse large cell lymphoma. As the management of low- and intermediate grade disease is so different biopsy proof of the nature of the relapse is of value. The prognostic factors identified need to be taken into consideration when analyzing results from trials of secondary treatment so as to avoid erroneous conclusions about comparative treatment efficacy.

Adolescent↗
PubMed1996

"MECCA": a developmental, dose-intensive, non-cross-resistant platinum-based chemotherapy for advanced ovarian cancer.

Twenty-nine women, ages 30-58 years, with advanced ovarian carcinoma were treated with a developmental combination chemotherapy regimen consisting of mitomycin C, etoposide, cisplatin, and carboplatin (MECCA). This protocol utilized the concepts of dose intensity, front-end loading, non-cross-resistance, and synergy. The median overall survival was 37 months with a 27% 5-year survival; the median failure-free survival was 15 months with a 14% 5-year failure-free rate. The predominant toxicity was hematologic and there was one toxic death (cardiac failure). The overall survival results are superior to our previous experience.

Adult↗
PubMed1996

Taxol is active in platinum-resistant endometrial adenocarcinoma.

Taxol, 170 mg/m2 by 3-h infusion every 3 weeks, was administered to seven patients with primarily advanced or recurrent endometrial cancer with progressive disease on platinum analogues. By standard response criteria, there were three clinical responders (43%; 95% confidence limits, 6-80%) and one disease stabilization. All three responses were clinical partial responses. The response duration ranged from 3 to 7 months. These preliminary results suggest that taxol is active in patients with platinum-resistant endometrial adenocarcinoma.

Adenocarcinoma↗
PubMed1995

Small cell carcinoma of the cervix treated with concurrent radiotherapy, cisplatin, and etoposide.

A multimodality regimen of four cycles of cisplatin and etoposide with concurrent locoregional radiotherapy (XRT) has been, since May 1988, the standard therapy for women with small cell carcinoma of the cervix (SCCC). Prophylactic cranial irradiation was to be used in all but primary progressors. All 11 patients (median age 47; 4 with pure SCCC and 7 with mixed histology) seen by us were treated with this regimen. Only 1 patient progressed while on treatment. The 3-year overall and failure-free survivals were 28%. Four patients remain alive in first remission; the remaining 7 died (2 from toxicity, 5 from cancer). Although not statistically significant due to the small numbers, it appeared that the chance of long-term survival depended both on the amount of the cancer as indicated by the FIGO stage and size of the primary and also the performance status. The toxicity was significant with 70% experiencing severe neutropenia and 40% being admitted for control of emesis. This regimen is only appropriate for those women in whom all of the apparent tumor can be encompassed within a radiation field and who, in addition, have a performance status of 0 or 1. For the remainder it does not offer any chance of long-term survival and its toxicity renders it antipalliative.

Adult↗
PubMed1994

Oral etoposide is active against platinum-resistant epithelial ovarian cancer.

PURPOSE: To determine whether etoposide (VP16) is more effective when administered on a chronic schedule, women with clinically defined platinum-resistant epithelial ovarian cancer (EOC) were studied. PATIENTS AND METHODS: Thirty-one eligible women were treated with oral VP16. The first seven received a dose that varied depending on their body-surface area, but this proved too toxic, and so a fixed dose of 100 mg orally per day for 14 days every 3 weeks was used for the other subjects. RESULTS: The response rate was 26% (95% confidence interval [CI], 11% to 41%). The 28 women with cancer that had progressed while they were receiving a platinum analog had a response rate of 21% (95% CI, 6% to 36%). Response durations were short. CONCLUSION: When administered on this chronic schedule, VP16 has activity against platinum-resistant EOC.

Administration, Oral↗
PubMed1992

Ten-year outcome of patients with advanced epithelial ovarian carcinoma treated with cisplatin-based multimodality therapy.

PURPOSE: At the end of the 1970s it was thought that advanced epithelial ovarian cancer (EOC) could be cured by multimodality treatment using surgery, cisplatin-based combination chemotherapy, and radiotherapy (RT). Such multimodality treatment was used as standard therapy at our institution. Our long-term results are reviewed. PATIENTS AND METHODS: One hundred ninety-five previously untreated patients with stage III or IV EOC were treated between April 1979 and December 1982. All patients were to have debulking surgery, when feasible, followed by the administration of doxorubicin and cisplatin at 50 mg/m2 every 3 weeks until a total dose of doxorubicin of 450 mg/m2 had been reached. RT was used in addition in patients with disease remaining after the chemotherapy. Maintenance chemotherapy with oral cyclophosphamide and hexamethylmelamine (altretamine) was administered to patients who did not have a documented histologic complete remission. RESULTS: The 10-year overall and failure-free survivals were 4% and 8%, respectively. The median overall survival was 2 years. The achievement of a histologic complete response (n = 32) did not equate to cure because 20 (63%) of the patients eventually relapsed. Multivariate analysis identified residual disease of greater or less than 2 cm as the only independent prognostic factor. CONCLUSIONS: Our multimodality treatment program was noncurative for the majority of the patients. Innovative therapies are needed before we can hope to cure such disease.

Adult↗
PubMed1991

Prognostic variables in patients with diffuse large-cell lymphoma treated with MACOP-B.

One hundred twenty-six patients with diffuse large-cell lymphoma were treated with methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between April 1981 and June 1986. Univariate and multivariate analyses were performed using overall survival as of September 1989 as the end point. Four independent negative predictors of survival were identified: presence of B symptoms; more than two involved lymph node sites; more than one extranodal site (variables related to tumor burden), and age older than 60, a variable related to the patient's ability to tolerate treatment. Each variable contributed the same relative risk of dying and, accordingly, this simple predictive formula was developed empirically: (4-N) x 30 = the approximate percentage of chance of survival at 5 years. "N" is the number of predictive variables present. The same four predictors were also found to be significant by multivariate analysis when only those patients achieving a complete response were analyzed.

Adolescent↗
PubMed1987

Chlorpropamide alcohol flushing: a normal response?

The relationship between chlorpropamide alcohol flushing and non-insulin dependent diabetes remains uncertain. It is known, however, that the frequency of facial flushing with alcohol and the temperature response depend upon both the plasma level of chlorpropamide and the starting facial temperature [10]. We tested 23 young adult non-diabetic subjects with 8 g of ethanol after a dose of chlorpropamide 250 mg twice daily for 2 days or a placebo, in a double blind, cross-over manner. Previously, nine other subjects had participated in a pilot study to assess the safety of the chlorpropamide dose and to ensure that adequate plasma chlorpropamide levels were achieved. No subject was negative for chlorpropamide alcohol flushing, as defined by the following criteria: facial temperature rise of 35% or more of maximum possible rise, observer assessment or subject assessment. In 26 of the total 32 subjects, all three criteria were fulfilled. Thus, among young, healthy non-diabetic adults chlorpropamide alcohol flushing would appear to be a normal phenomenon.

Adult↗
PubMed1986

Immune changes associated with insulin dependent diabetes may remit without causing the disease: a study in identical twins.

Activation of T lymphocytes and islet cell antibodies were studied in two groups of insulin dependent diabetics and their non-diabetic identical cotwins. Group 1 comprised 12 "short term" twin pairs (diabetic twin diagnosed less than five years previously) in whom only a third of the cotwins were likely to develop diabetes; 10 of the 12 non-diabetic cotwins showed increased values of activated T lymphocytes, islet cell antibodies, or both. Group 2 comprised 10 "long term" twin pairs (diabetic twin diagnosed more than 11 years previously) in whom none of the non-diabetic cotwins was likely to develop diabetes; these pairs were selected because all the non-diabetic cotwins had shown islet cell antibodies at some time in the past, but only two still did so (one with an increased value of activated T cells). There was relative glucose intolerance in the cotwins of the short term group but not in those of the long term group. Non-diabetic cotwins of diabetics may show the immune changes associated with insulin dependent diabetes and relative glucose intolerance, but these changes may remit without leading to diabetes.

Adolescent↗
PubMed1985

Value of insulin autoantibodies as serum markers for insulin-dependent diabetes mellitus.

Insulin autoantibodies (IAA) were studied in newly diagnosed insulin-dependent diabetics before the start of insulin treatment and in unaffected identical twins of insulin-dependent diabetics. In 15 of the 40 (38%) diabetics and 27 of the 58 (47%) twins IAA levels exceeded those of 100 controls. Frequency of IAA in unaffected twins was not related to duration of diabetes in their affected twin. In 11 unaffected twins, IAA levels differed in two samples taken 1-12 years apart; IAA were detected at least once in all twins and in one on both occasions. IAA in the twins were not related to the presence of islet-cell antibodies or to HLA-DR 3 or 4. As the unaffected twins of longstanding diabetics are unlikely to develop diabetes, these observations suggest that IAA do not always presage diabetes and are probably not a consequence of the disease; they may reflect an inherited autoimmune tendency to diabetes.

Adolescent↗
PubMed1985

Height at diagnosis of diabetes in children: a study in identical twins.

The height at diagnosis of 16 insulin dependent diabetics aged under 19 was compared with that of their unaffected identical cotwins measured at the same time. In eight pairs the diabetic was shorter, and in the remainder the cotwins were the same height. In those diabetics who were shorter than their cotwins at diagnosis the average period of growth delay before diagnosis was at least 35 weeks; by contrast, the mean duration of symptoms was only six weeks. No cause for the growth delay other than the diabetes was known in any of the twins. These findings show that the onset of insulin dependent diabetes may be a slow process, with growth delay occurring several months before symptoms appear.

Adolescent↗