British journal of cancer
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British journal of cancer · Mar 2000
Randomized Controlled Trial Clinical TrialA randomized phase III study comparing dacarbazine, BCNU, cisplatin and tamoxifen with dacarbazine and interferon in advanced melanoma.
The purpose of this study was to compare the response rate, overall and 1-year survival in patients with advanced melanoma treated with a standard therapy, dacarbazine and interferon-alpha (DTIC/IFN), or combination chemotherapy, consisting of dacarbazine, BCNU, cisplatin and tamoxifen (DBCT). Treatment toxicity and time spent in hospital were secondary end points. One hundred and five patients (of whom 100 were eligible) were randomized to receive either DTIC/IFN or DBCT. ⋯ DBCT was associated with significantly greater haematological toxicity, and a greater need for time spent in hospital (5.75 days/treatment cycle vs 2.29 with dacarbazine and interferon). DBCT combination therapy cannot be recommended as standard treatment for advanced melanoma. Dacarbazine remains the standard chemotherapy for this condition.
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British journal of cancer · Feb 2000
Development and validation of the Cancer Dyspnoea Scale: a multidimensional, brief, self-rating scale.
Dyspnoea is one of the most frequent and refractory symptoms in cancer patients. Lack of an appropriate assessment tool for dyspnoea seems to disturb establishment of management strategy. The purpose of this study was to develop and validate a brief self-rating scale to assess the multidimensional nature of dyspnoea in cancer patients. ⋯ Convergent validity, confirmed by a relation to Visual Analogue Scale of dyspnoea and modified Borg's scale, was also good (average: r= 0.57 and 0.52, respectively, and both P < 0.001). The CDS had good internal consistency (average Cronbach's alpha = 0.86) and stability (average test-retest reliability r = 0.66, P < 0.005). The present study demonstrated that the CDS is a brief, valid and feasible scale for assessing the multidimensional nature of dyspnoea in cancer patients.
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British journal of cancer · Feb 2000
Multicenter Study Clinical TrialImmunochemotherapy with interleukin-2, interferon-alpha and 5-fluorouracil for progressive metastatic renal cell carcinoma: a multicenter phase II study. Dutch Immunotherapy Working Party.
In patients with metastatic renal cell carcinoma response rates of 7-26% have been achieved with immunotherapy. A high response rate of 48% in 35 patients has been reported for treatment with the combination of interferon-alpha (IFN-alpha), interleukin-2 (IL-2) and 5-fluorouracil (5-FU) (Atzpodien et al (1993a) Eur J Cancer29A: S6-8). We conducted a multicentre phase II study to confirm these results. ⋯ Grade 3/4 toxicity (WHO) occurred in 29/52 (55.8%) of the patients in cycle 1 and in 6/16 (37.5%) of the patients in cycle 2. It consisted mainly of anorexia, fatigue, nausea, fever and leucocytopenia. We cannot confirm the high response rate in patients with metastatic renal cell carcinoma treated with the combination of IFN-alpha, IL-2 and 5-FU, as described by Atzpodien et al.
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British journal of cancer · Feb 2000
Clinical TrialEarly evaluation of tumour metabolic response using [18F]fluorodeoxyglucose and positron emission tomography: a pilot study following the phase II chemotherapy schedule for temozolomide in recurrent high-grade gliomas.
Quantitation of metabolic changes in tumours may provide an objective measure of clinical and subclinical response to anticancer therapy. This pilot study assesses the value of quantitation of metabolic rate of glucose (MRGlu) measured in mmol min(-1) ml(-1) to assess early subclinical response to therapy in a relatively non-responsive tumour. Nine patients receiving the CRC Phase II study schedule of temozolomide were assessed with [18F]fluorodeoxyglucose ([18F]FDG) dynamic positron emission tomography (PET) scans prior to and 14 days after treatment with temozolomide given as 750-1000 mg m(-2) over 5 days every 28 days. ⋯ Large differences also occurred in the normal brain SUV following treatment. Thus, MRGlu appeared to be a more sensitive discriminator of response than the simplified static SUV analysis. Changes in MRGlu may reflect the degree of cell kill following chemotherapy and so may provide an objective, quantitative subclinical measure of response to therapy.
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British journal of cancer · Feb 2000
Individuals with presumably hereditary uveal melanoma do not harbour germline mutations in the coding regions of either the P16INK4A, P14ARF or cdk4 genes.
In familial cutaneous malignant melanoma (CMM), disruption of the retinoblastoma (pRB) pathway frequently occurs through inactivating mutations in the p16 (p16INK4A/CDKN2A/MTS1) gene or activating mutations in the G1-specific cyclin dependent kinase 4 gene (CDK4). Uveal malignant melanoma (UMM) also occurs in a familial setting, or sometimes in association with familial or sporadic CMM. Molecular studies of sporadic UMM have revealed somatic deletions covering the INK4A-ARF locus (encoding P16INK4A and P14ARF) in a large proportion of tumours. ⋯ We screened by polymerase chain reaction single-strand conformation polymorphism the entire coding sequence of the INK4A-ARF locus (exon 1alpha from p16INK4A, exon 1beta from p14ARF, and exons 2 and 3, common to both genes), as well as the exons 2, 5 and 8 of the CDK4 gene, coding for the functional domains involved in p16 and/or cyclin D1 binding. A previously reported polymorphism in exon 3 of the INK4A-ARF locus was found in one patient affected with bilateral UMM, but no germline mutations were detected, either in the p16INK4A, p14ARF or CDK4 genes. Our data support the involvement of other genes in predisposition to uveal melanoma.