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J Shamash

Publications and source records attributed to J Shamash.

At least 37 records · Page 2Linked to original sources

Low-dose continuous chemotherapy (LBCMVD-56) for refractory and relapsing lymphoma.

BACKGROUND: Although lymphoid malignancies are generally chemosensitive, relapse is common. The use of high-dose therapy can make subsequent cytotoxic therapy intolerable. There is a need to develop regimens with low acute toxicity which are suitable for use in patients post-high dose therapy and following the failure of standard protocols. PATIENTS AND METHODS: Twenty-six patients with lymphomas, fifteen of whom had received high-dose therapy, were treated with a novel regimen consisting of low-dose lomustine, chlorambucil, daily subcutaneous bleomycin, vincristine and methotrexate with dexamethasone on an eight-week cycle (LBCMVD-56). A median of three cycles was given. RESULTS: The overall response rate at 12 weeks was 67% (21% complete remission (CR)) with a median overall survival of 13 months. A symptomatic response was seen in 72%. Previous high-dose therapy did not compromise the response rate. Toxicity was acceptable with grade 3-4 haematological toxicity seen in 27% of cycles, gastrointestinal toxicity seen in 11% and pulmonary toxicity seen in 8%. Thirty-one percent of patients required hospitalisation at some point during this treatment most commonly for neutropenic sepsis. CONCLUSIONS: LBCMVD-56 is an inexpensive, outpatient-based regimen with low acute toxicity and a high response rate in this heavily pre-treated group of patients.

Adolescent↗

Patterns of relapse and subsequent management following high-dose chemotherapy with autologous haematopoietic support in relapsed or refractory Hodgkin's lymphoma: a two centre study.

BACKGROUND: High-dose chemotherapy has an established role in recurrent or refractory Hodgkin's lymphoma (HL) although a significant proportion of patients subsequently relapse. This manuscript describes the clinical characteristics of such patients and documents their further management at two major UK cancer centres. PATIENTS AND METHODS: Between 1987 and 1996 one hundred patients with recurrent or refractory HL received high-dose chemotherapy (HDCT) with autologous haematopoietic rescue. All had recurred within 12 months of initial therapy or had two or more recurrences. RESULTS: With a median follow-up of 2 years, 56 patients are currently progression-free. There were six treatment-related deaths. One patient died of pneumonia in remission. Thirty-seven patients have relapsed, intrapulmonary disease being seen for the first time in 53% and recurrence at previous sites of disease in 81%. Following recurrence, therapy was determined by circumstances: either one agent at a time was used (single sequential approach) or multiagent chemotherapy was chosen. There was a survival advantage for those who achieved a symptomatic response (13 vs. 4 months median, P = 0.0001). A trend towards longer survival was seen for those whose disease recurred beyond six months following high-dose chemotherapy and in those who received combination chemotherapy. CONCLUSIONS: These results confirm that HDCT with autologous haematopoietic support is inadequate for about half the patients who receive it for high-risk HL. Relapse in the site of prior disease is the most likely pattern with intrapulmonary disease for the first time occurring frequently. It is possible to administer further chemotherapy after failure of HDCT, and both objective as well as subjective benefit can be achieved. A few patients appear to get long-term benefit from further treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Should high-dose chemotherapy be used to consolidate second or third line treatment in relapsing germ cell tumours?

Thirty consecutive patients with relapsing germ cell tumours (GCT) were treated with induction chemotherapy and high-dose chemotherapy consolidation (HDCT). Overall, 47% were progressionfree and 53% were alive with a median follow up of 40 months. Initially, HDCT was given as consolidation of third line VIP (etoposide/ifosfamide and cisplatin), following failure of a weekly cisplatin regimen. During 1995, paclitaxel was introduced into second line therapy with cisplatin and ifosfamide (TIP), with immediate consolidation using HDCT. At the same time the carboplatin dosing calculation was changed and an area under the curve (AUC) formula rather than by mg/m2 was used to calculate this. The main determinant of post-treatment renal dysfunction was pretreatment renal function rather than the AUC dose of carboplatin. Only a raised LDH prior to induction or absolute refractory disease in response to induction chemotherapy predicted poor survival following HDCT. In patients relapsing following HDCT, the outcome was poor with many patients relapsing in the central nervous system and other new sites of disease. Further responses were seen to chemotherapy or radiotherapy but these were not sustained. The failure to improve results when HDCT was used as second line rather than third line chemotherapy consolidation was disappointing and adds to further uncertainty of the role of this approach as far as timing and the ideal preparative regimen are concerned.

Adolescent↗

Sixty percent salvage rate for germ-cell tumours using sequential m-BOP, surgery and ifosfamide-based chemotherapy.

BACKGROUND: In germ-cell tumours (GCT), there is continuing controversy over the relative merits of dose dense therapy (increased frequency over a given time) versus vertical intensification (increased dose per fraction). The value of using a cisplatin-based dose dense approach in the salvage setting has not been documented and in addition the role of methotrexate remains uncertain. This paper reviews results from our investigations of these issues. PATIENTS AND METHODS: Between 1987 and 1996, 65 patients with relapsing or refractory germ-cell tumour received weekly m-BOP (methotrexate, bleomycin, vincristine and cisplatin) as salvage therapy. Residual masses were excised if possible and patients progressing after this received cisplatin and ifosfamide based chemotheraphy with or without high dose chemotherapy (HDCT) consolidation. RESULTS: With a median follow-up of 33 months, 34% are progression free following m-BOP, 11% who had surgery for residual masses which showed viable cancers are progression free. A further 15% who progressed following m-BOP with or without surgery were rendered progression free by third-line therapy. CONCLUSIONS: The use of m-BOP as second line therapy with deferment of cisplatin and ifosfamide based treatment to third line therapy with consolidation of third line responses with HDCT, leads to an overall progression-free survival of 60%. It does not appear that M-BOP prejudiced the response to third line therapy suggesting a lack of cross resistance. The potentially lower risk of leukaemia and infertility from m-BOP requires further evaluation.

Adolescent↗

Asymptomatic carotid arterial disease in young patients following neck radiation therapy for Hodgkin lymphoma.

PURPOSE: To determine the prevalence and severity of asymptomatic carotid arterial disease in young patients following neck radiation therapy for Hodgkin lymphoma and to compare the prevalence of carotid arterial disease following radiation therapy alone with that following radiation therapy and chemotherapy. MATERIALS AND METHODS: Forty-two survivors of childhood or early adult Hodgkin lymphoma aged 18-37 years who had undergone radiation therapy more than 5 years earlier underwent carotid arterial ultrasonography. Common carotid intima-media thickness was measured; carotid vessels were assessed for intima-media abnormalities. Results were compared with those from 33 control subjects. RESULTS: Patients had a significantly greater number of abnormal scans than did control subjects (11 [26%] vs one [3%]; P < .01). Ten patients (24%) had intima-media abnormalities that did not cause significant stenosis; one patient had diffuse bilateral intima-media thickening (mean, 1.99 mm) with greater than 70% stenosis of both common carotid arteries. Intima-media thickness was significantly greater in patients (0.51 mm) than in control subjects (0.43 mm; P < .005). The number of abnormalities in patients with radiation therapy plus chemotherapy (six [19%] of 31 patients) did not differ significantly from the number in patients with only radiation therapy (five [45%] of 11 patients; P = .12); there was no significant difference between median intima-media thicknesses (0.50 mm vs 0.51 mm, P > .2). CONCLUSION: Asymptomatic carotid arterial disease occurs frequently in young patients following neck radiation therapy for Hodgkin lymphoma. No difference in prevalence was shown between only radiation therapy and radiation therapy plus chemotherapy.

Adolescent↗

In vitro testing of calcium channel blockers and cytotoxic chemotherapy in B-cell low-grade non-Hodgkin's lymphoma.

The flux of calcium forms an important intracellular messenger system. The bcl-2 oncoprotein is thought to make cells resistant to a variety of insults, including cytotoxic drugs, by the suppression of apoptosis, which appears to involve the repartitioning of intracellular calcium. Three drugs that affect calcium pathways and may influence this repartitioning, i.e. dantrolene, azumolene (a water-soluble dantrolene analogue) and nimodipine, were studied in cell culture, using both a transformed follicle centre lymphoma cell line and primary culture of lymphoma cells in vitro in a manner that resulted in a growth pattern closely resembling that of the malignancy in vivo. Dantrolene and azumolene were potent inducers of cell death in both systems reducing the viable cell count by 70-90% in comparison with normal controls. Nimodipine, in comparison, appeared to have no significant effect. These results obtained in an in vitro setting suggest that further evaluation of dantrolene and azumolene for the treatment of low-grade non-Hodgkin's lymphoma is warranted.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Spying at work.

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Employment↗

Larger units best.

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Health Care Reform↗