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Aron Goldhirsch

Publications and source records attributed to Aron Goldhirsch.

63 records · Page 4Linked to original sources
PubMed2002

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↗
PubMedDate not supplied

Breast cancer.

Breast cancer remains a public-health issue on a global scale. We report new information about the disease from the past 5 years. Early age at first birth, increasing parity, and tamoxifen use are related to long-term lifetime reduction in breast-cancer risk. Ductal carcinomas in situ has been suggested to be renamed ductal intraepithelial neoplasia to emphasise its non-life-threatening nature. An alternative approach, the progenitor/stem cell theory, predicts that only some tumour cells cause cancer progression and that these should be targeted by treatment. Mammography and ultrasonography are still the most effective for women with non-dense and dense breast tissues, respectively. Additionally, MRI, lymphatic mapping, the nipple-sparing mastectomy, partial breast irradiation, neoadjuvant systemic therapy, and adjuvant treatments are promising for subgroups of breast-cancer patients. Although tamoxifen can be offered for endocrine-responsive disease, aromatase inhibitors are increasingly used. Assessment of potential molecular targets is now important in primary diagnosis. Tyrosine-kinase inhibitors and other drugs with anti-angiogenesis properties are currently undergoing preclinical investigations.

Breast Neoplasms↗
PubMedDate not supplied

Relation between chemotherapy dose, oestrogen receptor expression, and body-mass index.

Clinicians often reduce chemotherapy doses when treating obese patients because of concerns about overdosing. We assessed dose-response according to body-mass index (BMI) and oestrogen receptor (ER) expression of the primary tumour in premenopausal patients with node-positive breast cancer treated with classical CMF (cyclophosphamide, methotrexate, and 5-fluorouracil). Obese patients were significantly more likely to receive a lower chemotherapy dose (<85% of expected dose) for the first course than were those with normal or intermediate BMI (39%vs 16%, p<0.0001). For obese patients and for the total population, reducing the dose of chemotherapy was associated with a significantly worse outcome for the ER-negative cohort (total population hazards ratio 85%vs <85% 0.68 [95% CI 0.54-0.86] for disease free survival; 0.72 [0.56-0.94] for overall survival) but not for the ER-positive cohort (1.16 [0.97-1.40] for disease-free survival; 1.16 [0.94-1.44] for overall survival) [interaction p values=0.0001 for disease-free survival and 0.0019 for overall survival]. Our findings suggest that for women with ER-absent or ER-low tumours, reduction in chemotherapy dose should be avoided.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Intrathecal chemotherapy in carcinomatous meningitis from breast cancer.

UNLABELLED: Meningeal metastases occur in 2-3% of patients with breast cancer, leading to neurological morbidity and increased mortality. The criteria for treatment choice are controversial and intrathecal chemotherapy (ITC) has no documented role in the management of this disorder. We therefore evaluated the efficacy of an ITC regimen for patients presenting with carcinomatous meningitis from breast cancer. PATIENTS AND METHODS: Patients with meningeal carcinomatosis with or without concomitant parenchymal brain metastasis, were treated with repeated courses of intrathecal chemotherapy according to the following alternated weekly schedule: Day 1: Thiotepa 10 mg, methotrexate 15 mg, hydrocortisone 30 mg; Day 5: cytarabine (Ara-C) 70 mg, methotrexate 15 mg, hydrocortisone 30 mg. Folinic acid 15 mg was given orally, every six hours after methotrexate on days 2-3 and 6-7. RESULTS: Thirteen consecutive patients were treated. The median age was 45 (range 30-67) years. Eleven patients had performance status (PS) 2-3. Nine patients had other metastatic sites; synchronous parenchymal brain metastasis were present in 5 patients. Concomitant systemic chemotherapy was administered in 5 patients and external whole brain radiotherapy in 7 patients. With 12 evaluable patients we observed no responses or improvement in symptoms. Side-effects were minimal. CONCLUSION: In our series of patients, ITC failed to provide objective response or relief in clinical symptoms. Despite evidence reported in the literature indicating symptomatic improvement after ITC in a number of patients with leptomeningeal metastasis, the results of our study confirm the controversial role of ITC. New drugs and new modalities of treatment should be studied in order to efficiently control meningeal involvement of breast cancer.

Adult↗