Octreotide as first-line treatment for women with metastatic breast cancer

Summary Octreotide is a synthetic somatostatin analogue which has shown inhibitory activity against human breast cancer cells in culture. Ten patients with metastatic breast cancer and no prior hormonal therapy exposure received octreotide at 150 g subcutaneously thrice daily. No objective responses were observed and the median time to treatment failure was short at 57 days.     

Epidemic outbreak of interstitial lung disease in aerographics textile workers--the "Ardystil syndrome": a first year follow up.

BACKGROUND: The longer term respiratory effects of massive inhalational exposure of textile printing sprayers to Acramin (the "Ardystil syndrome") are not well established. METHODS: A 12 month follow up of 27 heavily exposed textile sprayers was performed. RESULTS: Twenty one patients experienced cough, 18 dyspnoea, and 17 nose bleeding at initial exposure, with histological evidence of organising pneumonia in 13 cases, radiological abnormalities detected by computed tomographic scanning in 20 cases, and diminution of diffusion capacity to below 80% of predicted in seven cases. At one year after exposure symptoms persisted in 15 cases, radiological alterations in six, and diffusion capacity was reduced in nine. CONCLUSIONS: Whilst most of our patients showed improvement at one year, evidence of persistent lung involvement was present in an appreciable minority of exposed cases.     

Primary intraosseous rhabdomyosarcoma

We report a case of primary intraosseous pleiomorphic rhabdomyosarcoma located in the pelvis of a 21-year-old woman followed for 4 years. The lytic tumor involved the acetabulum and the isthma with moderate extension to soft tissue. First line chemotherapy was unable to arrest tumor progression. Hemipelvectomy with saddle prosthesis reconstruction was performed, but septic complications dictated a secondary inter-ilio-abdominal amputation. Recurrence-free remission was achieved for 4 years, suggesting this was indeed a primary tumor. Primary intraosseous rhabdomyosarcomas are exceptional. Bone localizations generally suggest metastasis from a primary tumor often situated in an intraperitoneal localization. When search for a primary tumor is negative, intraosseous lesions can be considered as primary tumors warranting curative treatment. Radical surgical resection is recommended within the framework of a multidiscipinary management protocol associating radiotherapy and chemotherapy to improve prognosis.     

Post-traumatic aneurysm of humeral artery

Aneurysms are uncommon in the pediatric age-group. Unlike adults, in which aneurysms appear after alteration of the arterial wall due to systemic diseases, in children the traumatic etiology has to be considered: blunt trauma may disrupt the arterial wall and cause false aneurysm (pseudoaneurysm). Most aneurysms are asymptomatic, or they present as a pulsatile mass on an arterial traject. Diagnosis is confirmed with Doppler ultrasound and angiography. We present the case of a girl who, after blunt trauma of the right upper limb developed a pulsatile mass on the traject of the right humeral artery. Doppler ultrasound and angiography confirmed aneurysm of the humeral artery. She was successfully treated with surgical resection of the aneurysm and reconstruction of the arterial wall.     

Dose-dense regimen of temozolomide given every other week in patients with primary central nervous system tumors.

BACKGROUND: Temozolomide has shown activity and limited toxicity in patients with primary brain tumors at doses of 150-200 mg/m(2)/day on days 1-5 every 4 weeks. In this study, a new alternative dose-dense regimen of temozolomide was explored in patients with recurrent brain tumors. PATIENTS AND METHODS: In this study, we evaluated the safety, dose-limiting toxicity, maximum tolerated dose, recommended dose and activity of temozolomide given on days 1-3 and 14-16 every 28 days (one cycle). The starting daily dose was 200 mg/m(2) in a group of at least six patients, with subsequent increments of 50 mg/m(2) in groups of at least 12 patients until unacceptable toxicity was reached. Oral ondansetron (8 mg) was given 1 h prior to temozolomide administration. McDonald's criteria were used to evaluate antitumor activity. RESULTS: Seventy patients with brain tumors entered this study. The median number of prior chemotherapy treatments was two (range 1-3). Patients were assigned to one of four groups to receive temozolomide at daily doses of 200 (seven patients), 250 (13 patients), 300 (38 patients) and 350 mg/m(2)/day (12 patients). The absence of dose-limiting toxicity at cycle 1 led us to establish dose recommendations based on toxicity after repeated cycles. A total of 23, 72, 192 and 83 cycles were given at daily doses of 200, 250, 300 and 350 mg/m(2), respectively. Grade 3-4 thrombocytopenia was observed in 0/7, 1/13, 5/38 and 4/12 patients treated at doses of 200, 250, 300 and 350 mg/m(2)/day, respectively. Grade 3-4 neutropenia was observed in 1/7, 0/13, 3/38 and 4/12 patients treated with 200, 250, 300 and 350 mg/m(2)/day temozolomide, respectively. At a dose of 350 mg/m(2), sustained grade 2-3 thrombocytopenia did not allow treatment to be resumed at day 14 in >40% of patients, and this dose was considered to be the maximum tolerated dose. Thus, a dose of 300 mg/m(2)/day that was associated with <20% treatment delay due to sustained hematological toxicity was considered as the recommended dose. Objective responses were reported in 13 patients. CONCLUSIONS: Temozolomide can be given safely using a dose-dense regimen of 300 mg/m(2)/day for 3 consecutive days every 2 weeks in patients with recurrent brain tumors.     

Pilot study evaluating the pharmacokinetics, pharmacodynamics, and safety of the combination of exemestane and tamoxifen.

PURPOSE: We conducted a pilot study assessing the effects of the selective estrogen receptor modulator, tamoxifen, on the pharmacokinetics, pharmacodynamics, and safety of the steroidal, irreversible aromatase inhibitor (AI), exemestane, when the two were coadministered in postmenopausal women with metastatic breast cancer. EXPERIMENTAL DESIGN: Patients with documented or unknown hormone receptor sensitivity were eligible. Patients received oral exemestane at 25-mg once daily. Starting day 15, oral tamoxifen at 20-mg once daily, was added. We measured plasma concentrations of exemestane, estrone, estrone sulfate, and estradiol after 14 days of exemestane monotherapy and after approximately 4 weeks of combination therapy. The incidence and severity of adverse events were assessed by physical examination and patient reporting. RESULTS: We treated 18 patients. All had received prior chemotherapy and/or hormonal therapy, eight and six, respectively, with single-agent selective estrogen receptor modulators or irreversible aromatase inhibitors; no hormonal therapy was given within 30 days of study entry. Plasma exemestane concentrations and estrone, estrone sulfate, and estradiol suppression were unchanged after approximately 4 weeks of tamoxifen coadministration. All drug-related adverse events were grades 1 or 2; none was unexpected. Although not a formal study end point, antitumor activity was noted, with two partial responses and four cases of stable disease among 17 evaluable patients after a 9-month median follow-up (range, 2.5-19 months). CONCLUSIONS: This pilot study provides evidence that coadministration of tamoxifen does not affect exemestane pharmacokinetics or pharmacodynamics and that the combination is well-tolerated and active. Further clinical investigation is warranted.     

Continuous care in the cancer patient: palliative care in the 21<Superscript>st</Superscript> century

Continuous care for the cancer patient is an open concept that is not only applicable only to the terminal stage. Such a simplification could generate inequities of therapy and discrimination. Historically, oncology services have been structured as networks dispensing chemotherapy and radiotherapy rather than services dedicated to the integrated care of the cancer patient. This situation has changed in a continuous and progressive manner over the past few years, as reflected in the latest Spanish Libro Blanco de Oncología. We are still far from reaching the optimum level of integrated care, possibly because we have not, as yet, achieved services that are structured and appropriate for the care-needs of the patient and, perhaps, to the lack of the necessary personnel. We must always make sure that cancer patients receive the best possible treatment, irrespective of whet-her the disease is in relapse. Oncologists must not “give up”, indicating that, in addition to using the most effective anticancer treatments available, they should deploy their best knowledge and experience to control the symptoms of cancer while providing psycho-social help to the patient and family. This is best conducted with a communication that is adjusted to the changing needs of the patient over the longterm clinical process, and should be provided by a multidisciplinary team, according to the needs of the patient and the family. Within a program of integrated care, it is possible to coordinate the existing care structures without creating parallel health networks so as to cover the needs of the greatest number of cancer patients in advanced stage of the disease.     

Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years' follow-Up.

PURPOSE: To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy (RT) followed by surgery and postoperative flurouracil (FU)/leucovorin (LV) in patients with rectal cancer. PATIENTS AND METHODS: Patients (n = 94) with potentially resectable tumors, ultrasound at stages T2N+ (n = 4), T3 (n = 77), T4 (n = 13) were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV. Primary end points included downstaging, pathologic responses, and sphincter-preserving surgery. Secondary end points were recurrence-free survival and overall survival. RESULTS: All patients received the full RT dose. Fifteen patients (16%) needed UFT dose reduction. Preoperative G3+ toxicities included diarrhea (14%), leukopenia (1%), thrombocytopenia (1%), and nausea (4%). The downstaging rate was 54%, pathologic complete response (pCR) was 9% and, in an additional 23%, there were only residual microscopic foci. When cellular viability criteria were taken into account, the pCR was 15%. From 43 patients with abdominoperineal resection indication, 11 (25%) had sphincter-preserving surgery performed. Postoperative scheduled chemotherapy dose was not administered to 24% of patients because of G3+ toxicity (diarrhea, 8%; mucositis, 9%; and leukopenia, 7%). Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without. At 3 years, actuarial patterns of failure were pelvic, 5% and distant, 11%. OS was 75%. CONCLUSION: UFT combined with RT is safe and effective. In resectable rectal cancer, if preoperative treatment is considered, this approach can be an option.     

Expression and activity of CYP2E1 in circulating lymphocytes are not altered in diabetic individuals

Cytochrome P4502E1 (CYP2E1) plays an important role in ROS production thus favouring accelerated membrane lipid peroxidation. This isoform is strongly expressed in the liver but it can be also found in lymphocytes. As such, lymphocyte may provide a non-invasive accessible pool for screening CYP2E1 expression in man. We have, therefore, analysed CYP2E1 expression and activity in lymphocyte microsomes from 12 healthy controls, 11 type 1 and 12 type 2 diabetic subjects by using Western blot and enzymatic activities. Immunoblotting did not show difference among CYP2E1 protein bands in controls, type 1 and type 2 diabetics. To assess CYP2E1 activity we used the 7-ethoxy-4-trifluoromethylcoumarin (7-EFC), as a fluorescent substrate. The rate of deethylation of 7-EFC from controls did not differ from type 1 and type 2 diabetic subjects. The lack of any difference in CYP2E1 activity also was confirmed by the NADPH-dependent microsomal lipid peroxidation CCL4-induced assay showing similar peroxidation rates among controls and diabetic subjects. The results show that CYP2E1 expression/activity in lymphocytes is not enhanced in diabetes.