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Biomedical subjects

K D Swenerton

Publications and source records attributed to K D Swenerton.

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↗
PubMed2000

Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results.

BACKGROUND: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. METHODS: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. CONCLUSIONS: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.

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

Gliomatosis peritonei with malignant transformation.

A 13-year-old girl underwent a right salpingo-o-ophorectomy and partial omentectomy for an ovarian tumor that on microscopic examination was a grade 1 immature teratoma. Mature glial implants were found in the omentum (Stage III). No additional treatment was given. Ten months later, grade 0 and grade 1 peritoneal glial implants were found on laparotomy. Chemotherapy with four cycles of vincristine/cisplatin/etoposide/bleomycin was administered. A second laparotomy 4 months later showed persistence of grade 0 and grade 1 peritoneal glial implants. The patient was well for the next 7 years, after which time she presented with a pelvic mass that on microscopic examination was a malignant neuroectodermal tumor resembling a glioblastoma multiforme. The tumor did not respond to debulking and chemotherapy, and the patient died 6 months later, 8 years after her initial presentation. This case represents the second report of malignant transformation of peritoneal glial implants.

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

Endometrial adenocarcinoma presenting as an isolated calcaneal metastasis. A rare entity with good prognosis.

A 59-year-old woman presented with progressive pain, swelling, and erythema of her right foot. Biopsy of a destructive calcaneal lesion revealed a metastatic adenoacanthoma with focal adenosquamous carcinoma consistent with an endometrial origin. This was confirmed on hysterectomy. Postoperative treatment consisted of systemic chemotherapy, hormonal therapy, and local radiotherapy to the foot. She has now experienced 5 years of complete remission. This is a case of an endometrial adenocarcinoma presenting as an isolated calcaneal metastasis with an excellent outcome.

Adenocarcinoma↗
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↗
PubMed1994

European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion.

PURPOSE: Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT) is a new anticancer agent with activity in a number of human tumors, including epithelial ovarian cancer. In nonrandomized trials, doses studied have ranged from 135 mg/m2 to 250 mg/m2 administered over 24 hours with premedication to avoid hypersensitivity reactions (HSRs). This study addressed two questions: the dose-response relationship of Taxol in relapsed ovarian cancer and the safety of a short infusion given with premedication. METHODS: Women with platinum-pretreated epithelial ovarian cancer and measurable recurrent disease were randomized in a bifactorial design to receive either 175 or 135 mg/m2 of Taxol over either 24 or 3 hours. Major end points were the frequency of significant HSRs and objective response rate. Secondary end points were progression-free and overall survival. RESULTS: Of 407 patients randomized, 391 were eligible and 382 assessable for response. Analysis was performed according to the bifactorial design. Severe HSRs were rare (1.5% patients) and were not affected by either dose or schedule. Response was slightly higher at the 175-mg/m2 dose (20%) than at 135 mg/m2 (15%), but this was not statistically significant (P = .2). However, progression-free survival was significantly longer in the high-dose group (19 v 14 weeks; P = .02). Significantly more neutropenia was seen when Taxol was administered as a 24-hour infusion. Response rates were similar in the 24- and 3-hour groups (19% and 16%, respectively; P = .6). No survival differences were noted. CONCLUSION: The 3-hour infusion of Taxol is safe when given with premedication and is associated with less neutropenia. There is a modest dose effect with longer time to progression at 175 mg/m2. The observation that longer infusion produces more myelosuppression but does not yield higher response rates should lead to further studies to determine the optimal dose and schedule of this interesting new agent.

Adult↗
PubMed1994

Modeling toxicity and response in carboplatin-based combination chemotherapy.

Data from women with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III or IV) were analyzed to evaluate the pharmacokinetic/pharmacodynamic relationships of carboplatin-based combination chemotherapy. With the equation area under the plasma concentration versus time curve (AUC) = dose/(creatinine clearance + 25), carboplatin AUC was calculated in each of up to six treatment cycles in 224 women with advanced ovarian cancer who had been randomized to receive carboplatin 300 mg/m2 plus cyclophosphamide 600 mg/m2. In addition, for each patient, the predicted nadir count (obtained by rearranging the University of Maryland single-agent carboplatin dosing formula) was compared with the actual observed nadir count, received and relative received dose intensities were calculated, and carboplatin exposure intensity was defined. Relationships were sought between these treatment indices and the clinical outcomes of time to progression and survival. When combined with cyclophosphamide 600 mg/m2, any carboplatin AUC was found to be associated with greater myelotoxicity and a higher likelihood of both leukopenia and thrombocytopenia occurring than had been determined for single-agent carboplatin. Furthermore, the platelet nadir in 83% of patients was equal to or below that predicted to result from the same dose of single-agent carboplatin. There was a relatively narrow range of received dose intensities within this patient population, but carboplatin exposure intensity was calculated as being distributed over a two-fold range within the population. Therefore, received carboplatin dose intensity underestimates the range of plasma drug exposure associated with a fixed dosing regimen of carboplatin. However, there were no consistent relationships between received dose intensity, relative received dose intensity, or carboplatin exposure intensity and the clinical outcomes of time to progression or survival. The relationships between carboplatin exposure and the pharmacodynamic measures of toxicity and response are likely to require definition in each regimen that includes carboplatin and for each tumor type treated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Impact of cyclophosphamide on relationships between carboplatin exposure and response or toxicity when used in the treatment of advanced ovarian cancer.

PURPOSE: To determine (1) the impact of cyclophosphamide 600 mg/m2 on previously defined relationships between carboplatin area under the plasma concentration versus time curve (AUC) and indices of toxicity and response in women with advanced ovarian cancer; and (2) the relationships between indices of cumulative drug exposure and clinical outcomes. METHODS: Carboplatin AUC = dose/(creatinine clearance [CCr] + 25) and was calculated in 224 women who received carboplatin 300 mg/m2 and cyclophosphamide 600 mg/m2. The likelihood of grade 3 or greater myelotoxicity at any carboplatin AUC was compared with the likelihood of myelotoxicity at the same single-agent carboplatin AUC. The nadir count predicted using the University of Maryland single-agent carboplatin dosing formula was compared with the nadir count observed. Received and relative-received dose-intensity were calculated. Carboplatin exposure-intensity was defined by substituting cumulative carboplatin exposure for total dose. Relationships were sought between these indices and therapeutic outcomes. RESULTS: The incidence of leukopenia and thrombocytopenia at any carboplatin AUC was greater for the two-drug combination than for single-agent carboplatin. The platelet nadir in 83% of patients was less than or equal to the nadir predicted for the same single-agent carboplatin AUC. Despite a narrow range of received dose-intensities, carboplatin exposure-intensity was distributed over a twofold range. There were no relationships between received and relative-received dose-intensity or carboplatin exposure-intensity and time to progression or survival. CONCLUSION: Any carboplatin AUC when administered with cyclophosphamide 600 mg/m2 produces greater myelotoxicity than the same AUC of single-agent carboplatin. Received carboplatin dose-intensity underestimates the range of plasma drug exposure resulting from a fixed carboplatin dosing regimen. Whether higher carboplatin exposures can improve outcome requires prospective validation.

Adult↗
PubMed1992

Prognostic indices in ovarian cancer. Their significance in treatment planning.

Ovarian cancer exhibits a wide spectrum of behavior, the effectiveness of therapies varies and the circumstances of patients differ. Better outcomes will require more selective treatment strategies considerate of these variables. 1. The need for treatment As long as outcome is affected more by disease than by treatment, survival will be determined by the bulk and growth-rate of residual tumor-prognostic factors reflect these. They indicate the need for treatment, but not whether benefit is likely. FIGO stage is the international standard, but this alone is inadequately predictive. Grade reflects virulence, but subjectivity has limited its usefulness. Newer quantitative pathology techniques (such as DNA ploidy) more reproducibly reflect behavior. Prognostic factors can be used to define subsets of patients at differing degrees of disease risk. 2. Efficacy of treatment No response predictors are yet of practical use in selecting primary chemotherapy on an individual basis. Generally, response is more likely if the tumor is less extensive and if dose and treatment frequency are higher. Monitoring biomarkers can more quickly identify those with a suboptimal response who may require a change or discontinuation of treatment. Re-laparotomy has limited usefulness. Response predictors for second-line treatment (e.g. the failure-free interval) are available and also have implications for new drug testing. 3. Suitability of treatment Advanced age or serious additional illness may render intensive treatment inappropriate. The informed patient's wishes are of prime importance. An evolving strategy of selective management is described.

Antineoplastic Combined Chemotherapy Protocols↗
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↗
PubMed1992

Carboplatin in the treatment of carcinoma of the ovary: the National Cancer Institute of Canada experience. Ovarian Cancer Subcommittee.

The National Cancer Institute of Canada Clinical Trials Group has used carboplatin in two studies in women with ovarian carcinoma. In a phase II study, carboplatin produced a clinical response rate of 28% among patients with tumor persistence or recurrence following one prior cisplatin-containing regimen. Carboplatin was most efficacious in those with smaller tumors, in those who had the best responses to prior cisplatin therapy, and in those with longer intervals between the primary cisplatin treatment and the secondary carboplatin course. In this setting, a starting dose of 320 mg/m2 is suggested. A phase III randomized trial of first-line therapy compared the efficacy of cyclophosphamide/cisplatin with cyclophosphamide/carboplatin. Four hundred eighteen eligible patients were enrolled. The regimens demonstrated comparable efficacy; however, the carboplatin-based regimen was more easily administered and caused less symptomatic toxicity. The long-term results in this population with macroscopic residual disease remain disappointing.

Antineoplastic Combined Chemotherapy Protocols↗