Biomedical subjects

M Boente

Publications and source records attributed to M Boente.

5 recordsLinked to original sources

PubMed2001

Phase I trial of multiple cycles of high-dose carboplatin, paclitaxel, and topotecan with peripheral-blood stem-cell support as front-line therapy.

PURPOSE: To determine the safety and feasibility of delivering multiple cycles of front-line high-dose carboplatin, paclitaxel, and topotecan with peripheral-blood stem-cell (PBSC) support. PATIENTS AND METHODS: Patients were required to have a malignant solid tumor for which they had received no prior chemotherapy. Mobilization of PBSC was achieved with either filgrastim alone or in combination with cyclophosphamide and paclitaxel. Patients then received three or four cycles of high-dose carboplatin (area under the concentration-time curve [AUC] 16), paclitaxel (250 mg/m(2)), and topotecan (10-15 mg/m(2)), with the latter two agents administered as 24-hour infusions and supported with PBSC and filgrastim. Cycles were repeated every 28 days. RESULTS: Twenty patients were enrolled onto the trial and were assessable for toxicity and clinical outcome. Dose-limiting toxicities were stomatitis and prolonged hematopoietic recovery. The maximum-tolerated dose of topotecan was 12.5 mg/m(2) when given with high-dose carboplatin and paclitaxel for three cycles. Four cycles were able to be given with a dose of topotecan of 10 mg/m(2). The pharmacokinetics of each compound were not affected by the other agents. Eleven (85%) of 13 patients with assessable disease responded. CONCLUSION: Multiple cycles of high-dose carboplatin, paclitaxel, and topotecan can be safely administered with filgrastim and PBSC support. The recommended doses for phase II study are carboplatin AUC 16, paclitaxel 250 mg/m(2), and topotecan 10 mg/m(2). Trials are currently being conducted with this regimen as front-line treatment in patients with advanced ovarian cancer and extensive small-cell carcinoma. This approach remains experimental and should be used only in the context of a clinical trial.

Adult↗

PubMed1999

Phase I trial of multiple cycles of high-dose chemotherapy supported by autologous peripheral-blood stem cells.

PURPOSE: To determine the safety and feasibility of delivering multiple cycles of front-line high-dose carboplatin and paclitaxel with hematopoietic peripheral-blood stem cell (PBSC) support. PATIENTS AND METHODS: Patients were required to have a malignant solid tumor for which they had received no prior chemotherapy. Mobilization of PBSC was achieved with cyclophosphamide, etoposide, and granulocyte-macrophage colony-stimulating factor (GM-CSF). After one cycle of conventional-dose carboplatin and cyclophosphamide with GM-CSF, patients received multiple cycles of high-dose carboplatin (area under the concentration-time curve [AUC], 12 to 20) and paclitaxel (250 mg/m(2)) with PBSC and GM-CSF repeated every 28 days. RESULTS: Twenty-four of 28 patients were assessable for toxicity and clinical outcome. Dose-limiting toxicities were dehydration, diarrhea, and electrolyte imbalances. The maximum-tolerated dose of carboplatin was AUC 16 (equivalent to a median of 1,189 mg/m(2)). The relationship of target AUC to measured AUC was linear (r(2) =. 29; P =.0011). The overall response rate was 96%, with a complete clinical response rate of 67%. The median time to progression from the first PBSC reinfusion was 49.5 weeks (range, 8 to 156+ weeks). CONCLUSION: Multiple cycles of high-dose carboplatin (AUC 16) and paclitaxel (250 mg/m(2)) can be safely administered with GM-CSF and PBSC support. Although this regimen is safe, feasible, and active, the use of multiple cycles of high-dose chemotherapy as front-line treatment remains experimental and should only be used in the context of a clinical trial.

Adult↗

PubMed1998

Surgery for gynecologic malignancies.

Surgery continues to play a primary role in the investigation and treatment of gynecologic neoplasia. Cold-knife conization is still preferable for diagnosis and treatment of more problematic preinvasive cervical lesions. Newer reconstructive techniques can improve quality of life in exenteration patients. Efforts continue to reduce morbidity associated with vulvar surgery and groin node dissection. Accurate staging and maximum cytoreduction remain essential goals in primary surgery for ovarian cancers. The utility of secondary surgery for disease assessment or further treatment is controversial. Laparoscopy at present has a limited role in gynecologic oncology but may be useful for prophylactic oophorectomy in selected individuals.

Endometrial Neoplasms↗

PubMed1996

Improved outcome in patients treated with postoperative radiation therapy for pathologic stage I/II endometrial cancer.

PURPOSE: To evaluate prognostic factors and treatment outcome for high risk pathological Stage I and II endometrial cancer patients treated with consistent postoperative radiation therapy (RT) in a single institution and to compare these results to series where RT was variably applied. METHODS AND MATERIAL: Between 1986 and 1993, 98 pathologic Stage I and II endometrial cancer patients received postoperative RT at the Fox Chase Cancer Center. Papillary serous and clear cell histologies were excluded. Fifty-five patients underwent lymph node evaluation. In 17 patients, RT consisted of intracavitary brachytherapy alone to a median dose of 21 Gy, and in 81 patients, RT consisted of external beam RT to a median dose of 45 Gy followed by intracavitary brachytherapy to a median dose of 12 Gy. Intracavitary brachytherapy generally consisted of three high dose rate implants with the dose prescribed to a depth of 0.5 cm. Median follow up was 47 months. RESULTS: The 5-year overall survival (OS), disease free survival (DFS), and freedom from pelvic recurrence (FPR) rates were 83, 85, and 89%, respectively. Pelvic recurrence either as the sole pattern of failure or combined with distant metastases was seen in 2 and 7% of patients, respectively. Distant metastases alone occurred in 4% of the patients. Univariate analysis of prognostic factors including age, grade, capillary lymphatic space invasion, depth of myometrial invasion, type of lymph node evaluation, pathologic stage, the use of brachytherapy and the number of risk factors was performed for OS, DFS, FPR, and FDM. Capillary lymphatic space invasion was the only statistically significant predictor for reduced DFS. Absence of lymph node dissection as well as a higher number of risk factors showed a trend toward poorer DFS (p = 0.06 for both). Multivariate analysis revealed older age to be the only factor significant for reduced DFS, with the presence of capillary lymphatic space invasion and the absence of a lymph node dissection showing a trend toward poorer outcome (p = 0.07). CONCLUSIONS: The results of this study suggest a continued role for the use of postoperative RT in the treatment of patients with high risk endometrial cancer and will be compared to other series with similar high-risk factors.

Adult↗

PubMed1994

Recurrent ovarian cancer. Effective radiotherapeutic palliation after chemotherapy failure.

BACKGROUND: Recurrent ovarian cancer after frontline chemotherapy is incurable; however, palliation of focal lesions often is needed to alleviate symptoms. Because published response rates to palliative irradiation (RT) among patients failing cisplatin-based chemotherapy are scarce, the authors attempted to define the palliative role of radiotherapy for symptomatic, localized ovarian cancer recurrences. Factors predicting a response to RT also were sought. METHODS: Between 1987 and 1993, 33 patients with ovarian cancer were irradiated at 47 sites with palliative intent after failing cisplatin-based chemotherapy regimens. Sites irradiated included the pelvis (n = 33), abdomen (n = 5), chest (n = 4), brain (n = 3), and other (n = 2). Median RT dose was 35 Gy (range: 7.5-45 Gy). The median fraction size was 2.5 Gy (range, 1-5 Gy). To determine dose effectiveness, the biologic effective dose (BED) was calculated according to the following formula: BED = total dose (1 + fractional dose/alpha/beta) using an alpha/beta value of 10. The median BED10 was 44 (range, 9-72). RESULTS: For the entire group, complete palliative response was 51% and overall palliative response was 79%. The median duration of palliation was 4 months, which reflected palliation until death in 90% of cases. The overall response rates by symptoms were: pulmonary symptom relief in 75%, vaginal bleeding control in 90%, rectal bleeding control in 85%, pain relief in 83%, and neurologic symptoms controlled in 50%. The likelihood of obtaining complete symptomatic response was significantly increased among those with high Karnofsky performance status (KPS > or = 70 vs. KPS < 70; 69% vs. 36%, P < 0.03) and among those who received a higher biologically effective dose of irradiation (BED10 > or = 44 vs. BED10 < 44; 68% vs 35%, P < 0.03). Complete palliative response rates were not influenced by histologic differentiation, the number of previously administered cisplatin regimens, or patient age. Treatment-related acute morbidities included diarrhea in 5 of 38 (13%) patients treated through abdominal or pelvic fields, and esophagitis in 2 of 5 treated through thoracic portals. Only one severe late morbidity (small bowel obstruction) was observed. CONCLUSIONS: Durable palliation of patients with ovarian cancer that recurs after cisplatin-based chemotherapy can be achieved with local radiotherapy, especially among patients with high performance status. Biologically effective doses of at least 44 Gy10 (e.g., 3500 cGy/14 fractions = BED10 of 44) should be sought to maximize the probability of complete response. Such dose-fractionation schedules can be delivered expeditiously with acceptable tolerance. These results are comparable to the published experience of second-line chemotherapy in the treatment of focally symptomatic ovarian cancer recurrences.

Age Factors↗