British journal of cancer
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British journal of cancer · Jul 2002
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialA double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer.
Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor. Recent advances in conventional chemotherapy and the development of novel 'molecular' treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies. This randomised study in pancreatic cancer compares marimastat (orally administered matrix metalloproteinase inhibitor) in combination with gemcitabine to gemcitabine alone. ⋯ The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer. The combination of marimastat with gemcitabine was well tolerated. Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified.
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British journal of cancer · Jul 2002
Randomized Controlled Trial Clinical TrialImmune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes.
Besides cytotoxicity, taxanes induce other biological effects, especially in the immune system. Taxanes have demonstrated immunostimulatory effects against neoplasms, supporting the idea that these agents suppress cancer through several mechanisms and not solely through inhibiting cell division. The purpose of the present study was to evaluate the effect of taxanes (paclitaxel and docetaxel) and investigate their ability in alterating important immunological parameters in breast cancer patients. ⋯ More specifically, docetaxel demonstrated a more pronounced effect on enhancing MLR, NK, LAK activity and IFN-gamma, IL-2, IL-6, and GM-CSF levels, as well as caused more potent reduction in IL-1 and TNF-alpha levels when compared to paclitaxel. The present study indicates that patients responded to treatment of advanced breast cancer with single-agent paclitaxel or docetaxel leads to an increase in serum IFN-gamma, IL-2, IL-6, GM-CSF cytokine levels and enhancement of PBMC NK and LAK cell activity, while they both lead to a decrease of acute phase serum cytokine levels of IL-1 and TNF-alpha. Moreover, the effects of docetaxel are in all the above parameters more pronounced than those of paclitaxel.
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British journal of cancer · Jun 2002
Adjuvant androgen deprivation impacts late rectal toxicity after conformal radiotherapy of prostate carcinoma.
To evaluate whether androgen deprivation impacts late rectal toxicity in patients with localised prostate carcinoma treated with three-dimensional conformal radiotherapy. One hundred and eighty-two consecutive patients treated with 3DCRT between 1995 and 1999 at our Institution and with at least 12 months follow-up were analysed. three-dimensional conformal radiotherapy consisted in 70-76 Gy delivered with a conformal 3-field arrangement to the prostate+/-seminal vesicles. As part of treatment, 117 patients (64%) received neo-adjuvant and concomitant androgen deprivation while 88 (48.4%) patients were continued on androgen deprivation at the end of three-dimensional conformal radiotherapy as well. ⋯ A multivariate analysis identified the use of adjuvant androgen deprivation (P=0.0196) along with the dose to the posterior wall of the rectum on the central axis (P=0.0055) and the grade of acute rectal toxicity (P=0.0172) as independent predictors of grade 2-4 late rectal toxicity. The 2-year estimates of grade 2-4 late rectal toxicity for patients receiving or not adjuvant hormonal treatment were 30.3+/-5.2% and 14.1+/-3.8%, respectively. Rectal tolerance is reduced in presence of adjuvant androgen deprivation.
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British journal of cancer · Jun 2002
ReviewWhich endpoints should we use in evaluating the use of novel fluoropyrimidine regimens in colorectal cancer?
Although significant advances have been made in the treatment of advanced/metastatic colorectal cancer, 5-fluorouracil (5-FU) still forms the basis of chemotherapy. Recently, new 5-FU schedules and novel fluoropyrimidines have been developed, but there are no trials directly comparing these regimens. The current review describes the mechanisms of action, pre-clinical and phase I/II studies of two oral fluoropyrimidine therapies, capecitabine and uracil with tegafur plus leucovorin. ⋯ All four new therapies demonstrated superior safety profiles compared with the Mayo Clinic regimen. However the uracil with tegafur plus leucovorin regimen was associated with severe diarrhoea and capecitabine with hand-foot syndrome. Patients will not sacrifice efficacy for the convenience of oral therapy alone, therefore the fact that capecitabine achieved superior response rates and equivalent time to disease progression compared with the Mayo Clinic regimen, while uracil with tegafur plus leucovorin produced lower response rates and significantly inferior time to disease progression, is highly relevant in choosing treatment.
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British journal of cancer · Jun 2002
Clinical Trial Controlled Clinical TrialClinical and economic benefits of irinotecan in combination with 5-fluorouracil and folinic acid as first line treatment of metastatic colorectal cancer.
The combination of irinotecan plus 5-fluorouracil and folinic acid has clinical and survival benefits over 5-fluorouracil and folinic acid alone in the setting of first line treatment of metastatic colorectal cancer. The aim of this cost-effectiveness analysis was to compare the economic implications, from a UK health commissioner perspective, of the two treatment arms (de Gramont regimen) in this setting. Resource utilisation data collected prospectively during the study were used as a basis for estimating cumulative drug dosage, chemotherapy administration, and treatment of complications during first line therapy. ⋯ Cumulative costs per patient associated with further chemotherapy were lower in the irinotecan plus 5-fluorouracil and folinic acid treatment arm. Based on incremental costs per life-year gained of 14 794 pounds sterling, the combination of irinotecan plus 5-fluorouracil and folinic acid can be considered cost-effective by commonly accepted criteria compared with 5-fluorouracil and folinic acid alone. Thus, clinical and economic data demonstrate that irinotecan, either in combination with irinotecan plus 5-fluorouracil and folinic acid in the first line setting or as monotherapy in the second line setting, has a major role in the management of metastatic colorectal cancer.