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Biomedical subjects

Bernhard C Pestalozzi

Publications and source records attributed to Bernhard C Pestalozzi.

13 recordsLinked to original sources

Potential use of humanized antibodies in the treatment of breast cancer.

With the growing knowledge of key cellular pathways in tumor induction and evolution, targeted therapies make up an increasing proportion of new drugs entering clinical testing. In the treatment of breast cancer, humanized antibodies have become a major option. The humanized monoclonal antibody trastuzumab (Herceptin); Genentech, Inc., CA, USA) for HER2-overexpressing, metastatic breast cancer, represents a successful agent associated with impressive survival benefits when combined with chemotherapy. Based on impressive results, trastuzumab will become a standard in the adjuvant treatment of HER2-overexpressing breast cancer. The role of trastuzumab in the neoadjuvant setting is promising, but must be further evaluated in large prospective, randomized trials. However, there is still a large proportion of patients overexpressing HER2 that do not respond to trastuzumab. Regarding this patient cohort, the optimal combination of trastuzumab with other agents needs further evaluation. In breast cancer lacking HER2 amplification, the role of the new antibody pertuzumab remains to be defined. The role of antibodies interfering with angiogenesis, tumor stroma or glycoproteins is of a preliminary nature and warrants further investigation. Here, an overview of humanized antibodies in human breast cancer is provided, with emphasis on the recent advances and future prospects in treating malignant breast cancer.

Antibodies, Monoclonal↗

Positron emission tomography/computed tomography influences on the management of resectable pancreatic cancer and its cost-effectiveness.

OBJECTIVE: We sought to determine the impact of positron emission tomography/computed tomography (PET/CT) on the management of presumed resectable pancreatic cancer and to assess the cost of this new staging procedure. SUMMARY BACKGROUND DATA: PET using 18F-fluorodeoxyglucose (FDG) is increasingly used for the staging of pancreatic cancer, but anatomic information is limited. Integrated PET/CT enables optimal anatomic delineation of PET findings and identification of FDG-negative lesions on computed tomography (CT) images and might improve preoperative staging. MATERIAL AND METHODS: Patients with suspected pancreatic cancer who had a PET/CT between June 2001 to April 2004 were entered into a prospective database. Routine staging included abdominal CT, chest x-ray, and CA 19-9 measurement. FDG-PET/CT was conducted according to a standardized protocol, and findings were confirmed by histology. Cost benefit analysis was performed based on charged cost of PET/CT and pancreatic resection and included the time frame of staging and surgery. RESULTS: Fifty-nine patients with a median age of 61 years (range, 40-80 years) were included in this analysis. Fifty-one patients had lesions in the head and 8 in the tail of the pancreas. The positive and negative predictive values for pancreatic cancer were 91% and 64%, respectively. PET/CT detected additional distant metastases in 5 and synchronous rectal cancer in 2 patients. PET/CT findings changed the management in 16% of patients with pancreatic cancer deemed resectable after routine staging (P = 0.031) and was cost saving. CONCLUSIONS: PET/CT represents an important staging procedure prior to pancreatic resection for cancer, since it significantly improves patient selection and is cost-effective.

Adenocarcinoma↗

Capecitabine with weekly paclitaxel for advanced breast cancer: a phase I dose-finding trial.

OBJECTIVE: To determine the maximum tolerated dose (MTD), toxicity and activity of combined weekly paclitaxel and capecitabine in patients with metastatic breast cancer. METHODS: Sixteen patients with metastatic breast cancer, of whom 15 were evaluable for toxicity and response, were enrolled in 7 Swiss centers. Paclitaxel 80 mg/m2 was given intravenously on days 1, 8 and 15. Capecitabine was administered orally on days 1 through 14 using five different dose levels. Both drugs were given in a 21-day schedule. RESULTS: Capecitabine could be administered at doses commonly used for the drug as a single agent, i.e. 1,250 mg/m2 twice daily in combination with weekly paclitaxel. Hematological and other toxicities did not appear to be dose-limiting; however, significant skin and nail toxicities were observed. A response or stable disease was observed in 87% of patients [13/15; exact 95% confidence interval (CI) 60-98%], with 2 complete responses, 4 partial responses (overall response rate 40%, exact 95% CI 16-68%) and 7 patients with stable disease for at least 9 weeks. CONCLUSION: The phase I evaluation of capecitabine in combination with fixed-dose weekly paclitaxel did not allow the definition of an MTD of capecitabine based on the predefined criteria. Instead, the dose for the phase II evaluation was determined based on the occurrence of toxicity in later courses and on experience with other regimens containing capecitabine. Capecitabine (1,000 mg/m2 twice daily, days 1-14, every 3 weeks) with paclitaxel (80 mg/m2 weekly) is a promising combination for advanced breast cancer now being investigated in a phase II trial.

Antimetabolites, Antineoplastic↗

Living donor liver transplantation and tolerance: a potential strategy in cholangiocarcinoma.

BACKGROUND: Donor-specific immune tolerance has been reported in isolated cases of kidney transplantation associated with bone marrow transplantation. The following is a description of a living donor liver transplantation for a hilar cholangiocarcinoma in a previous recipient of an allogeneic bone marrow transplant. METHOD: A right hemi-liver transplantation was performed using a liver allograft obtained from the same previous bone marrow donor. A neoadjuvant chemo-irradiation protocol was implemented before the procedure. Because of the presence of full chimerism, no immunosuppression has been necessary for the last 22 months. RESULTS: Liver graft function has remained excellent, and a magnetic resonance imaging scan at one and a half years has shown no tumor recurrence. A control liver biopsy at 1 year showed no rejection. CONCLUSIONS: Neoadjuvant chemo-irradiation therapy and removal of all immunosuppression after liver transplantation formed the basic structure of this approach. Additional benefits provided by living donor liver transplantation included limitation of tumor progression by diminishing the pretransplantation waiting time, radical excision of the tumor through a complete hepatectomy, and optimal timing of the transplant procedure within a neoadjuvant chemo-irradiation protocol.

Adult↗

Peritoneal carcinoma in a male patient.

Peritoneal carcinoma is a rare primary tumor, described in the literature almost exclusively in women. This report describes our clinicopathological findings in a 51-year-old male patient with peritoneal carcinoma and ascites. Pathologic studies included routine histology, immunohistochemistry and electron microscopy on biopsy and autopsy tumor tissue. After chemotherapy, the patient achieved a complete remission twice, lasting for 14 months and 8 months, respectively, and died after 3 years. His clinical course was similar to that of female patients with peritoneal carcinoma or advanced ovarian cancer. Our case confirms the existence of primary peritoneal carcinoma in males. In addition, it shows that this entity responds to the same chemotherapy as used for ovarian cancer and primary peritoneal carcinoma in females.

Ascites↗

Phase II study of capecitabine and oxaliplatin in first- and second-line treatment of advanced or metastatic colorectal cancer.

PURPOSE: To determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the treatment of advanced nonpretreated and pretreated colorectal cancer. PATIENTS AND METHODS: Forty-three nonpretreated patients and 26 patients who had experienced one fluoropyrimidine-containing regimen for advanced colorectal cancer were treated with oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1,250 mg/m(2) bid on days 1 to 14 every 3 weeks. Patients with good performance status (World Health Organization grade 0 to 1) were accrued onto two nonrandomized parallel arms of a phase II study. RESULTS: The objective response rate was 49% (95% confidence interval [CI], 33% to 65%) for nonpretreated and 15% (95% CI, 4% to 35%) for pretreated patients. The main toxicity of this combination was diarrhea, which occurred at grade 3 or 4 in 35% of the nonpretreated and 50% of the pretreated patients. Grade 3 or 4 sensory neuropathy, including laryngopharyngeal dysesthesia, occurred in 16% of patients on both cohorts. Capecitabine dose reductions were necessary in 26% of the nonpretreated and 45% of the pretreated patients in the second treatment cycle. The median overall survival was 17.1 months and 11.5 months, respectively. CONCLUSION: Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer. The main toxicity is diarrhea, which is manageable with appropriate dose reductions. On the basis of our toxicity experience, we recommend use of capecitabine in combination with oxaliplatin 130 mg/m(2) at an initial dose of 1,250 mg/m(2) bid in nonpretreated patients and at a dose of 1,000 mg/m(2) bid in pretreated patients.

Adenocarcinoma↗

Gemcitabine-related pulmonary toxicity.

BACKGROUND: Gemcitabine is an increasingly used and generally well tolerated anticancer drug. Rarely, it leads to potentially fatal pulmonary toxicity. CASE DESCRIPTIONS AND RESULTS: We describe the clinical features of 5 patients with gemcitabine-related pulmonary toxicity. Due to early diagnosis, prompt discontinuation of the drug, and treatment with steroids, toxicity was reversible in all cases. CONCLUSION: Early recognition of gemcitabine-related pulmonary toxicity is mandatory.

Aged↗

Gemcitabine-associated hemolytic-uremic syndrome.

BACKGROUND: Gemcitabine has mild renal toxicity, but cases of gemcitabine-associated hemolytic-uremic syndrome (HUS) have been reported. METHODS: A case is presented of a 45-year-old woman on prolonged gemcitabine treatment for ovarian cancer who developed HUS and recovered after drug discontinuation. A mini-review of the literature based on a MEDLINE search follows. RESULTS: Including our own patient, a total of 26 cases of gemcitabine-associated HUS were identified. Median patient age was 52 years. Treatment was for various tumors at advanced stages, and in some patients, other anticancer drugs previously had been administered. Mean time between initiation of gemcitabine therapy and onset of HUS was 7.4 +/- 3.5 months, or 21.9 +/- 10.9 doses of gemcitabine. The calculated median cumulative dose of gemcitabine was 20,000 mg/m(2) (range, 2,450 to 48,000 mg/m(2), or a total of 70,000 mg). The onset of disease was noted up to 2 months after the last gemcitabine infusion. Diagnosis of HUS was confirmed histologically in 13 patients and based on clinical findings in the other 15. Treatment included drug discontinuation, steroids, fresh frozen plasma, hemodialysis, absorption chromatography, plasmapheresis, and various combinations thereof. Of 23 patients with reported outcome, 11 died within a few weeks. In two cases, death was believed to be a direct consequence of HUS. Reexposure to the drug was reported in three patients but was uncomplicated in only one. CONCLUSION: There are only a few confirmed cases of gemcitabine-associated HUS despite the widespread use of the drug. This potentially fatal complication is difficult to treat and should be widely known.

Antimetabolites, Antineoplastic↗