22 results on '"McKendrick JJ"'
Search Results
2. High dose intensity combination chemotherapy for advanced epithelial ovarian carcinoma: results of a pilot study
- Author
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Sweetenham, JW, primary, McKendrick, JJ, additional, Jones, DH, additional, Whitehouse, JMA, additional, and Williams, CJ, additional
- Published
- 1990
- Full Text
- View/download PDF
3. Involvement of the ileocaecal region by non-Hodgkin's lymphoma in adults: clinical features and results of treatment.
- Author
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Sweetenham, JW, Mead, GM, Wright, DH, McKendrick, JJ, Jones, DH, Williams, CJ, Whitehouse, JMA, Sweetenham, J W, Mead, G M, Wright, D H, McKendrick, J J, Jones, D H, Williams, C J, and Whitehouse, J M
- Published
- 1989
- Full Text
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4. 4-(4-Hy-droxy-phenyl)-2,2,4-trimethyl-7,8-benzo-thia-chroman, a fused-ring counterpart of thia -Dianin's compound.
- Author
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Frampton CS, McKendrick JJ, and MacNicol DD
- Abstract
The title compound, C
22 H22 OS [systematic name: 4-(1,3,3-trimethyl-2,3-di-hydro-1 H -4-thia-phenanthren-1-yl)phenol], crystallizes unsolvated from nitro-methane as colourless prisms (m.p. 425-427 K) in the polar monoclinic space group Ia with Z ' = 2 (mol-ecules A and B ). Both independent mol-ecules possess a very similar proximal conformation, this referring to the juxtaposition of the 4-hy-droxy-phenyl substituent with respect to the syn -related methyl group. In the crystal, mol-ecule A is linked to mol-ecule B by an O-H⋯O hydrogen bond. In turn, mol-ecule B exhibits a weak O-H⋯π inter-action with the phenolic group of mol-ecule A related by a -glide symmetry. Together, these lead to [100] chains.- Published
- 2017
- Full Text
- View/download PDF
5. Survival Impact of Adjuvant Chemotherapy for Resected Locally Advanced Rectal Adenocarcinoma.
- Author
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Tay RY, Jamnagerwalla M, Steel M, Wong HL, McKendrick JJ, Faragher I, Kosmider S, Hastie I, Desai J, Tacey M, Gibbs P, and Wong R
- Subjects
- Adenocarcinoma pathology, Aged, Australia, Chemotherapy, Adjuvant methods, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Neoplasm Recurrence, Local, Proportional Hazards Models, Rectal Neoplasms pathology, Retrospective Studies, Survival Rate, Adenocarcinoma therapy, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Rectal Neoplasms therapy
- Abstract
Background: Recent data has created uncertainty regarding the benefit of adjuvant fluoropyrimidine-containing chemotherapy following preoperative chemoradiotherapy and surgical resection for locally advanced rectal cancer (LARC). In particular, patients with a pathologic complete response (pCR) may derive no benefit from adjuvant chemotherapy., Patients and Methods: This is a retrospective analysis of patients with LARC, diagnosed between January 1, 2003 and December 31, 2014 at 3 Melbourne health services. Patients were identified from the Australian Comprehensive Cancer Outcomes and Research Database, where a defined data set is prospectively collected on consecutive patients. Patient demographics, pCR rates, postoperative treatment, recurrence, and survival were analyzed., Results: A total of 717 patients with LARC were identified, of whom 555 (77%) had received preoperative long-course chemoradiation followed by surgery. Four hundred fifty-two of 555 patients (81%) subsequently received adjuvant fluoropyrimidine-based chemotherapy. At a median follow-up of 45.9 months, 95 (21%) patients in the adjuvant chemotherapy group and 20 (19%) in the surveillance group had relapsed. Five-year relapse-free survival was 77% in the adjuvant chemotherapy group and 71% in the surveillance group with no significant difference on univariate analysis (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.58-1.51; P = .780). No significant impact on relapse-free survival was seen for either pCR or non-pCR patients. Five-year overall survival (OS) was 85% in the adjuvant chemotherapy group and 74% in the surveillance group with a nonsignificant trend towards OS benefit (HR, 0.62; 95% CI, 0.37-1.05; P = .074). A significant OS benefit favoring adjuvant chemotherapy was seen in the non-pCR subset of patients (HR, 0.49; 95% CI, 0.28-0.86; P = .014)., Conclusion: A high proportion of patients in this routine practice cohort received adjuvant chemotherapy following preoperative treatment and surgery for LARC. Adjuvant chemotherapy administration was associated with a significant improvement in 5-year OS only in the patients with a non-pCR., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
6. Time course of safety and efficacy of aflibercept in combination with FOLFIRI in patients with metastatic colorectal cancer who progressed on previous oxaliplatin-based therapy.
- Author
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Ruff P, Ferry DR, Lakomỳ R, Prausová J, Van Hazel GA, Hoff PM, Cunningham D, Arnold D, Schmoll HJ, Moiseyenko VM, McKendrick JJ, Ten Tije AJ, Vishwanath RL, Bhargava P, Chevalier S, Macarulla T, and Van Cutsem E
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols pharmacology, Biomarkers, Pharmacological, Camptothecin adverse effects, Camptothecin pharmacology, Camptothecin therapeutic use, Colorectal Neoplasms pathology, Disease Progression, Disease-Free Survival, Female, Fluorouracil adverse effects, Fluorouracil pharmacology, Humans, Irinotecan, Leucovorin adverse effects, Leucovorin pharmacology, Male, Neoplasm Metastasis, Oxaliplatin, Proportional Hazards Models, Receptors, Vascular Endothelial Growth Factor adverse effects, Receptors, Vascular Endothelial Growth Factor pharmacology, Recombinant Fusion Proteins adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Camptothecin analogs & derivatives, Fluorouracil therapeutic use, Leucovorin therapeutic use, Organoplatinum Compounds therapeutic use, Receptors, Vascular Endothelial Growth Factor therapeutic use, Recombinant Fusion Proteins therapeutic use
- Abstract
Background: Patients with metastatic colorectal cancer (mCRC) previously-treated with oxaliplatin benefit significantly from the addition of aflibercept to FOLFIRI in relation to overall survival, progression-free survival and response rate., Patients and Methods: The results for efficacy and safety over the time course of the VEGF Trap (aflibercept) with irinotecan in colorectal cancer after failure of oxaliplatin regimen trial were analysed based on data from 1226 patients randomised to receive FOLFIRI plus either aflibercept (n=612) or placebo (n=614). Hazard ratios (HR) by 6-month time period were estimated using a piecewise Cox proportional hazard model. Severity of adverse events (AEs) was graded using National Cancer Institute Common Terminology Criteria, version 3.0., Results: The estimated probabilities of survival were 38.5% versus 30.9% at 18 months, 28.0% versus 18.7% at 24 months and 22.3% versus 12.0% at 30 months, for the aflibercept- and placebo-treated arms, respectively. The proportional improvement in the HR over time was consistent with the survival probability results; survival at 24 months was improved by 50% and almost doubled at 30 months. The majority of worst-grade AEs occurred within the first four cycles of treatment and in a small percent of treatment cycles and were mostly reversible. Common chemotherapy- and anti-vascular epithelial growth factor (VEGF)-associated AEs occurred rarely and in a small proportion of cycles with the majority being of single occurrence., Conclusions: The addition of aflibercept to FOLFIRI showed a continued and persistent improvement in overall survival over time in patients with mCRC. Although grade 3-4 AEs were more frequent in the aflibercept arm, they occurred in early treatment cycles and decreased sharply following initial presentation., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2015
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7. Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial.
- Author
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Tabernero J, Van Cutsem E, Lakomý R, Prausová J, Ruff P, van Hazel GA, Moiseyenko VM, Ferry DR, McKendrick JJ, Soussan-Lazard K, Chevalier S, and Allegra CJ
- Subjects
- Aged, Antibodies, Monoclonal, Humanized administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bevacizumab, Camptothecin administration & dosage, Camptothecin adverse effects, Camptothecin analogs & derivatives, Colorectal Neoplasms pathology, Diarrhea chemically induced, Double-Blind Method, Drug Administration Schedule, Fatigue chemically induced, Fluorouracil administration & dosage, Fluorouracil adverse effects, Humans, Irinotecan, Kaplan-Meier Estimate, Leucovorin administration & dosage, Leucovorin adverse effects, Middle Aged, Neoplasm Metastasis, Neutropenia chemically induced, Prospective Studies, Receptors, Vascular Endothelial Growth Factor administration & dosage, Receptors, Vascular Endothelial Growth Factor adverse effects, Recombinant Fusion Proteins administration & dosage, Recombinant Fusion Proteins adverse effects, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colorectal Neoplasms drug therapy
- Abstract
Purpose: The antiangiogenic agent aflibercept (ziv-aflibercept in the United States) in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) significantly improved survival in a phase III study of patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen. In the present analysis, outcomes were evaluated in prespecified subgroups to assess the consistency of the treatment effect., Methods: Patients were randomised to receive FOLFIRI plus aflibercept or placebo every 2weeks until disease progression or unacceptable toxicity occurred. Efficacy and safety outcomes were analysed with respect to demographic and baseline characteristics, and stratification factors (prior bevacizumab treatment and Eastern Cooperative Oncology Group performance status)., Results: Median overall survival (OS, months [95.34% confidence interval (CI)]) for aflibercept versus placebo was 12.5 (10.8-15.5) versus 11.7 (9.8-13.8) in patients with prior bevacizumab treatment and 13.9 (12.7-15.6) versus 12.4 (11.2-13.5) in patients with no prior bevacizumab treatment. The p value for interaction was 0.5668, indicating there was no heterogeneity in these subgroups. For OS and progression-free survival (PFS), there was a significantly greater benefit (at the 2-sided 10% level) of treatment for patients with liver only metastases versus patients with no liver metastases/liver metastases with other organ involvement (p value for interaction: 0.0899 [OS]; 0.0076 [PFS]). There was no evidence of heterogeneity in treatment effect in any of the other subgroups examined., Conclusions: The benefits of aflibercept in combination with FOLFIRI in patients with mCRC previously treated with oxaliplatin were maintained across the specified patient subgroups, including in patients with or without prior bevacizumab treatment., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2014
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8. Financial incentives in cancer care and impact on prescribing practice.
- Author
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Wong HL, Field KM, Shapiro JD, McKendrick JJ, and Gibbs P
- Subjects
- Aged, Australia, Capecitabine, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Deoxycytidine economics, Drug Prescriptions economics, Fluorouracil administration & dosage, Fluorouracil analogs & derivatives, Fluorouracil economics, Hospitals, Private economics, Hospitals, Public economics, Humans, Antineoplastic Agents administration & dosage, Antineoplastic Agents economics, Colorectal Neoplasms drug therapy, Colorectal Neoplasms economics
- Published
- 2013
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9. The anti-leukemic effect and molecular mechanisms of novel hydroxamate and benzamide histone deacetylase inhibitors with 5-aza-cytidine.
- Author
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Liu HB, Mayes PA, Perlmutter P, McKendrick JJ, and Dear AE
- Subjects
- Caspase 3 genetics, Cell Proliferation drug effects, Cyclin-Dependent Kinase Inhibitor p21 genetics, HL-60 Cells, Humans, Matrix Metalloproteinase 9 genetics, Nuclear Receptor Subfamily 4, Group A, Member 1 genetics, Antineoplastic Agents pharmacology, Azacitidine pharmacology, Benzamides pharmacology, Histone Deacetylase Inhibitors pharmacology, Hydroxamic Acids pharmacology, Leukemia drug therapy
- Abstract
Histone deacetylase inhibitors (HDACi) demonstrate considerable in vitro and in vivo activity and clinical efficacy in the treatment of hematological malignancies. Pre-clinical and early phase clinical trials identify therapeutic activity using a combination of HDACi and demethylating agents which may be more efficacious than single agent treatment. Our studies aimed to determine the effects and molecular mechanisms of action of novel hydroxamate (MCT-3) and benzamide [MGCD0103 (MG)] HDACi's in the HL-60 cell line alone and in combination with the demethylating agent 5-aza-cytidine (AZA). MG, MCT-3 and AZA treatment significantly inhibited HL-60 cell growth in vitro with MG being the most potent agent. MG in combination with AZA demonstrated no significant increase in inhibition of cell growth over MG treatment alone whilst MCT-3 in combination with AZA demonstrated increased inhibition of cell growth over either agent alone although no more significant than MG alone. MG alone or MCT-3 in combination with AZA significantly increased p15 and caspase-3 expression. MG and MCT-3 significantly attenuated AZA-induced MMP-9 mRNA expression and proteolytic activity. Interestingly, MCT-3, MG and AZA alone and in combination increased expression of the novel tumour suppressor gene Nur77, important in leukemogenesis, with MG a more potent inducer as a single agent. These observations suggest the enhanced anti-leukemia activity of the combination of AZA and HDACi may only reside with certain HDACi classes and may be in-part explained by regulation of genes associated with cell cycle arrest, apoptosis and tumour suppression.
- Published
- 2011
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10. The anti-leukemic effect of a novel histone deacetylase inhibitor MCT-1 and 5-aza-cytidine involves augmentation of Nur77 and inhibition of MMP-9 expression.
- Author
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Liu HB, Voso MT, Gumiero D, Duong J, McKendrick JJ, and Dear AE
- Subjects
- Apoptosis drug effects, Cyclin-Dependent Kinase Inhibitor p15 genetics, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, HL-60 Cells drug effects, Humans, Nuclear Receptor Subfamily 4, Group A, Member 1, RNA, Messenger genetics, RNA, Neoplasm genetics, RNA, Neoplasm isolation & purification, Reverse Transcriptase Polymerase Chain Reaction, Antimetabolites, Antineoplastic therapeutic use, Azacitidine therapeutic use, DNA-Binding Proteins genetics, Histone Deacetylase Inhibitors, Hydroxamic Acids therapeutic use, Leukemia drug therapy, Matrix Metalloproteinase 9 genetics, Receptors, Steroid genetics, Sulfonamides therapeutic use
- Abstract
A combination of demethylating agents and histone deacetylase inhibitors (HDACi) has been proposed as a novel therapy in leukemia and myelodysplasia. In HL-60 cells azacytidine (AZA) and Metacept-1 (MCT-1), a novel HDACi augmented inhibition of cell growth and increased apoptosis. In identifying a molecular mechanism responsible for these effects MCT-1 alone and in combination with AZA induced p15INK4b, p21WAF1/CIP1 and Caspase-3 whilst attenuating Bcl-XL expression. Interestingly, MCT-1 in combination with AZA significantly induced the recently identified suppressor of leukemogenesis Nur77 and attenuated AZA-induced MMP-9 expression. The combination of MCT-1 and AZA is more effective in inhibiting leukemic cell growth and induction of apoptosis. Regulation of a recently identified tumour suppressor gene together with cell cycle, apoptosis and matrix degrading proteases may underpin the molecular mechanism responsible for these effects.
- Published
- 2009
11. Detailed analysis of a randomized phase III trial: can the tolerability of capecitabine plus docetaxel be improved without compromising its survival advantage?
- Author
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Leonard R, O'Shaughnessy J, Vukelja S, Gorbounova V, Chan-Navarro CA, Maraninchi D, Barak-Wigler N, McKendrick JJ, Harker WG, Bexon AS, and Twelves C
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms mortality, Capecitabine, Carcinoma mortality, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Docetaxel, Dose-Response Relationship, Drug, Female, Fluorouracil administration & dosage, Fluorouracil adverse effects, Humans, Maximum Tolerated Dose, Middle Aged, Neoplasm Metastasis drug therapy, Survival Analysis, Taxoids administration & dosage, Treatment Outcome, Breast Neoplasms drug therapy, Carcinoma drug therapy, Deoxycytidine analogs & derivatives, Fluorouracil analogs & derivatives, Taxoids adverse effects
- Abstract
Background: In a phase III trial, 3-weekly capecitabine (1250 mg/m(2) twice daily days 1-14) plus docetaxel (75 mg/m(2) day 1) demonstrated significantly superior overall survival to 3-weekly docetaxel (100 mg/m(2) day 1). We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy., Patients and Methods: Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered., Results: More patients receiving capecitabine/docetaxel (65%) had dose reductions for adverse events than docetaxel alone (35%). In most patients requiring dose reduction with the combination (80%), capecitabine and docetaxel were simultaneously reduced to 950 mg/m(2) and 55 mg/m(2), respectively. Subsequently, there were fewer cycles (17%) with grade 3/4 adverse events than with the full doses (34%). Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles., Conclusions: Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy. This retrospective analysis, as well as multiple phase II studies of taxanes with reduced-dose capecitabine, shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer. In addition, reducing the dose of both agents may be appropriate.
- Published
- 2006
- Full Text
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12. Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial.
- Author
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Cassidy J, Douillard JY, Twelves C, McKendrick JJ, Scheithauer W, Bustová I, Johnston PG, Lesniewski-Kmak K, Jelic S, Fountzilas G, Coxon F, Díaz-Rubio E, Maughan TS, Malzyner A, Bertetto O, Beham A, Figer A, Dufour P, Patel KK, Cowell W, and Garrison LP
- Subjects
- Administration, Oral, Capecitabine, Chemotherapy, Adjuvant economics, Cost-Benefit Analysis, Deoxycytidine administration & dosage, Deoxycytidine economics, Disease-Free Survival, Drug Administration Schedule, Drug Costs statistics & numerical data, Fluorouracil administration & dosage, Health Care Costs, Health Resources statistics & numerical data, Humans, Injections, Intravenous, Leucovorin administration & dosage, Neoplasm Staging, Quality of Life, Remission Induction, Sensitivity and Specificity, Survival Rate, Time Factors, Treatment Outcome, United Kingdom, Antineoplastic Combined Chemotherapy Protocols economics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colonic Neoplasms drug therapy, Deoxycytidine analogs & derivatives, Fluorouracil economics, Leucovorin economics
- Abstract
Oral capecitabine (Xeloda) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings pound3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings pound1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK.
- Published
- 2006
- Full Text
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13. Multiple relapses of mature teratoma, germinal and non-germ cell cancer in a patient treated with chemotherapy for testicular non-seminomatous germ cell cancer.
- Author
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McKendrick JJ, Mead GM, and Cowlishaw D
- Subjects
- Antineoplastic Combined Chemotherapy Protocols administration & dosage, Bleomycin administration & dosage, Cisplatin administration & dosage, Etoposide administration & dosage, Humans, Male, Middle Aged, Neoplasm Metastasis, Neoplasms, Germ Cell and Embryonal surgery, Orchiectomy, Teratoma surgery, Testicular Neoplasms surgery, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lung Neoplasms secondary, Neoplasm Recurrence, Local, Neoplasms, Germ Cell and Embryonal drug therapy, Neoplasms, Germ Cell and Embryonal pathology, Peritoneal Neoplasms secondary, Teratoma drug therapy, Teratoma pathology, Testicular Neoplasms drug therapy, Testicular Neoplasms pathology
- Published
- 2003
- Full Text
- View/download PDF
14. Brain as sanctuary site of relapse in germ cell cancer patients previously treated with chemotherapy.
- Author
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Crabb SJ, McKendrick JJ, and Mead GM
- Subjects
- Adult, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Chorionic Gonadotropin analysis, Germinoma radiotherapy, Germinoma surgery, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Remission Induction, Survival Rate, Testicular Neoplasms drug therapy, Treatment Outcome, alpha-Fetoproteins analysis, Brain Neoplasms secondary, Germinoma secondary, Testicular Neoplasms pathology
- Abstract
Background: Post chemotherapy isolated relapse to the brain of germ cell cancer is potentially curable., Patients and Methods: We reviewed the experience of germ cell cancer with cerebral metastases at the CRC Wessex Medical Oncology Unit in Southampton. Patients were classified according to their presentation (initial diagnosis, solitary relapse or widespread). Treatment and outcome of these patients is presented and compared with previous series., Results: Of 1049 patients treated for metastatic germ cell cancer, 15 were diagnosed with cerebral metastases. Six patients had cerebral sanctuary site relapse, and underwent resection and cranial irradiation. Four of these are continuously disease free after treatment at 2, 67, 96, and 145 months from therapy, another is receiving chemotherapy for limited systemic relapse and the sixth has relapsed and died. Three further patients relapsed with cerebral disease in the presence of active disease elsewhere and each progressed and died. The final six patients had cerebral disease at presentation of whom five have progressed and died., Conclusions: Isolated cerebral metastases occurring after successful systemic chemotherapy for germ cell cancer are curable. An aggressive salvage approach with surgery followed by radiotherapy is indicated.
- Published
- 2002
- Full Text
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15. A phase I and pharmacokinetic study of subcutaneously-administered recombinant human interleukin-4 (rhuIL-4) in patients with advanced cancer.
- Author
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Davis ID, Maher DW, Cebon JS, Green MD, Fox RM, McKendrick JJ, Rybak ME, and Boyd AW
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- Adult, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Cytotoxicity, Immunologic, Escherichia coli genetics, Female, Humans, Injections, Subcutaneous, Interleukin-4 adverse effects, Interleukin-4 chemistry, Interleukin-4 pharmacology, Male, Middle Aged, Neoplasms immunology, Recombinant Proteins adverse effects, Recombinant Proteins chemistry, Recombinant Proteins pharmacokinetics, Recombinant Proteins pharmacology, Antineoplastic Agents pharmacokinetics, Interleukin-4 pharmacokinetics, Neoplasms drug therapy
- Abstract
Purpose: To investigate the pharmacokinetics and tolerability of recombinant human interleukin-4 (rhuIL-4), administered by daily subcutaneous injection, in patients with advanced cancer., Patients and Methods: Fourteen patients with advanced cancer treated with rhuIL-4 at escalating dose levels of 0.25, 1.0 and 5.0 microg/kg/day, on days 1, 8-17, and 28-57. The primary endpoints of the study were toxicity of rhuIL-4 and the determination of the pharmacokinetics of rhuIL-4 when given by subcutaneous injection. Secondary endpoints included effects on blood counts, hematopoietic cell precursors, and various immunologic parameters., Results: rhuIL-4 was well tolerated at all three dose levels. Detectable serum levels of IL-4 were found in patients at the 1.0 and 5.0 microg/kg/day dose levels. Peak serum IL-4 levels were achieved about 2 h after injection and IL-4 was still detectable 8 h after injection. No grade 4 toxicities were observed and grade 3 toxicities were confined to fever, headache and raised hepatic alkaline phosphatase. No consistent hematological or immunologic effects were observed. Although therapeutic efficacy was not an endpoint, one complete response (Hodgkin's disease) was observed. One patient with chronic lymphocytic leukemia progressed on therapy., Conclusion: rhuIL-4 up to 5.0 microg/kg/day is well tolerated when given by subcutaneous injection. Biologically relevant serum IL-4 levels can be achieved and sustained for at least 8 h after a single injection.
- Published
- 2000
- Full Text
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16. Two brothers with mediastinal tumours.
- Author
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Brown S and McKendrick JJ
- Subjects
- Endodermal Sinus Tumor genetics, Humans, Male, Middle Aged, Seminoma genetics, Mediastinal Neoplasms genetics, Neoplasms, Germ Cell and Embryonal genetics
- Published
- 1996
- Full Text
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17. Lean body mass, body surface area and epirubicin kinetics.
- Author
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Cosolo WC, Morgan DJ, Seeman E, Zimet AS, McKendrick JJ, and Zalcberg JR
- Subjects
- Body Mass Index, Epirubicin blood, Epirubicin toxicity, Humans, Neoplasms drug therapy, Neoplasms metabolism, Spectrophotometry, Atomic, Body Surface Area, Body Weight physiology, Epirubicin pharmacokinetics
- Abstract
For a number of cytotoxics, a relationship between efficacy and plasma concentrations has recently been demonstrated. Lean body mass has been demonstrated to be a useful parameter for predicting drug clearance for a number of non-cytotoxic drugs. However, the role of lean body mass in predicting drug clearance for any cytotoxic drug has not been previously reported. Our purpose was to investigate lean body mass as a predictor of epirubicin clearance. Pharmacokinetic studies were performed in 10 patients receiving single agent epirubicin. Although preliminary, this study suggests that lean body should be further evaluated and tested in dose optimization studies.
- Published
- 1994
- Full Text
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18. Assessment of proliferative responses to granulocyte-macrophage colony-stimulating factor (GM-CSF) in acute myeloid leukaemia using a fluorescent ligand for the nucleoside transporter.
- Author
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Wiley JS, Cebon JS, Jamieson GP, Szer J, Gibson J, Woodruff RK, McKendrick JJ, Sheridan WP, Biggs JC, and Snook MB
- Subjects
- Acute Disease, Blood Proteins analysis, Bone Marrow drug effects, Bone Marrow Cells, Cell Division drug effects, Humans, Leukemia, Megakaryoblastic, Acute drug therapy, Leukemia, Megakaryoblastic, Acute pathology, Nucleoside Transport Proteins, Thymidine metabolism, Tritium, Carrier Proteins analysis, Fluoresceins, Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use, Leukemia, Myeloid drug therapy, Leukemia, Myeloid pathology, Membrane Proteins analysis, Purine Nucleosides
- Abstract
Nucleoside transporter expression has been linked to proliferation in a variety of haemopoietic cell types. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was given for 72 h before commencing chemotherapy in 15 patients with relapsed or refractory acute myeloid leukaemia (AML) and in 11 patients serial bone marrows were taken for measurement of [3H]thymidine labelling index, Ki-67 positivity and maximal binding of 5-(SAENTA-x8)-fluorescein, a flow cytometry ligand which enumerates nucleoside transporter sites. GM-CSF caused proliferation of marrow myeloblasts in eight of 11 patients, while in three patients there was no change in proliferative indices. The expression of nucleoside transporters increased up to 4-fold in the myeloblasts from the patients showing a proliferative response to GM-CSF but there was no increase in transporters on the myeloblasts from the three non-responding patients. A close correlation was found between the fold increase in nucleoside transporter expression and the fold increase in labelling index of marrow myeloblasts (r = 0.86, n = 9, p < 0.01). In one patient with acute megakaryoblastic leukemia, GM-CSF caused parallel increases in labelling index, Ki-67 positivity and numbers of nucleoside transporters on peripheral blood blast cells. Thus induction of proliferation by cytokine increases the expression of nucleoside transporters on leukaemic myeloblasts studied in serial samples from the same source (bone marrow or blood). The suitability of 5-(SAENTA-x8)-fluorescein for two colour flow cytometric analysis allows the rapid enumeration of nucleoside transporters in the myeloblast compartment of heterogeneous marrow samples.
- Published
- 1994
19. Prednisolone, cytosine arabinoside, lomustine (CCNU), etoposide and thioguanine (PACET) combination chemotherapy for relapsed or refractory non-Hodgkin lymphoma.
- Author
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Sweetenham JW, McKendrick JJ, Mead GM, and Whitehouse JM
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cytarabine administration & dosage, Etoposide administration & dosage, Female, Humans, Lomustine administration & dosage, Male, Middle Aged, Neutropenia chemically induced, Prednisolone administration & dosage, Prognosis, Prospective Studies, Thioguanine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Non-Hodgkin drug therapy
- Abstract
27 patients with relapsed/refractory non-Hodgkin lymphoma (NHL) received combination chemotherapy with prednisolone, cytosine arabinoside, lomustine (CCNU), etoposide and thioguanine (PACET). 25 patients are evaluable for response. 7 (26%) obtained a complete response and one (4%) a partial response. The median survival for the entire group was 6 months. 2 patients are currently alive without disease, 1 of whom has received further therapy. The regimen was intensely myelosuppressive, but was well tolerated. The complete response rate and median survival figures are comparable to previous studies of salvage therapy confirming the poor prognosis for relapsed NHL and emphasising the need for prospective randomised studies.
- Published
- 1993
- Full Text
- View/download PDF
20. All-trans retinoic acid in the treatment of acute promyelocytic leukaemia.
- Author
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White KL, Wiley JS, Frost T, McKendrick JJ, Hermann RP, Seldon M, Enno A, Bell R, Bunce I, and Taylor K
- Subjects
- Adult, Australia, Cell Differentiation drug effects, Female, Humans, Leukemia, Promyelocytic, Acute blood, Leukemia, Promyelocytic, Acute pathology, Leukocyte Count, Male, Middle Aged, Remission Induction, Tretinoin adverse effects, Leukemia, Promyelocytic, Acute drug therapy, Tretinoin therapeutic use
- Abstract
All-trans-retinoic acid (ATRA) is known to induce differentiation of promyelocytes in vitro and also to induce remission of acute promyelocytic leukaemia in vivo. We treated 11 patients with poor prognosis acute promyelocytic leukaemia (APL) with ATRA and obtained seven complete and one partial remission. Remissions took one to three months to achieve and were associated with adverse effects including dry skin and bone pain. In eight patients the white cell count rose above 20 x 10(9)/L within the first ten days of retinoic acid treatment and this was associated with the development of pulmonary leukostasis in three patients which was fatal in one. Another two patients died of intracranial haemorrhage also within the first ten days. ATRA is a promising new agent in the induction therapy of this particular category of acute leukaemia.
- Published
- 1992
21. Nonseminomatous germ cell tumor with very high serum human chorionic gonadotropin.
- Author
-
McKendrick JJ, Theaker J, and Mead GM
- Subjects
- Adolescent, Adult, Brain Neoplasms secondary, Combined Modality Therapy, Humans, Lung Neoplasms secondary, Male, Middle Aged, Neoplasms, Germ Cell and Embryonal pathology, Neoplasms, Germ Cell and Embryonal secondary, Neoplasms, Germ Cell and Embryonal therapy, alpha-Fetoproteins analysis, Chorionic Gonadotropin blood, Neoplasms, Germ Cell and Embryonal blood
- Abstract
Most patients with disseminated nonseminomatous germ cell tumor (NSGCT) have an excellent prognosis with modern chemotherapy, although certain subgroups with a worse prognosis have been described. One such subgroup includes patients with high serum levels of the tumor marker, human chorionic gonadotropin (HCG). Sixteen patients of 104 treated for NSGCT at the CRC Wessex Medical Oncology Unit (Southampton, UK) presented with serum HCG greater than 25,000. Most of these patients exhibited features of the "choriocarcinoma syndrome" with bulky, rapidly progressive disease; frequent pulmonary, hepatic, and central nervous system complications; and a generally poorer response to standard NSGCT chemotherapy. Histologic identification of trophoblastic tumor was not made in all patients and is not essential for the diagnosis of the syndrome; indeed, closed biopsy may be contradicted in some circumstances because of the risk of hemorrhage. The NSGCT patients with poor prognosis, including patients with the choriocarcinoma syndrome, must be clearly identified in order to improve management and, eventually, cure rates.
- Published
- 1991
- Full Text
- View/download PDF
22. ChlVPP chemotherapy in advanced Hodgkin's disease.
- Author
-
McKendrick JJ, Mead GM, Sweetenham J, Jones DH, Williams CJ, Ryall R, and Whitehouse JM
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Chlorambucil administration & dosage, Chlorambucil adverse effects, Female, Humans, Male, Prednisolone administration & dosage, Prednisolone adverse effects, Procarbazine administration & dosage, Procarbazine adverse effects, Vinblastine administration & dosage, Vinblastine adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy
- Abstract
Between March 1978 and January 1987 54 patients with advanced Hodgkin's disease (HD) or relapse following radiotherapy (RT) for Hodgkin's disease have been treated with combination chemotherapy consisting of chlorambucil, vinblastine, procarbazine and prednisolone (ChlVPP). A subgroup of five patients with bulky mediastinal disease received mantle RT in addition to ChlVPP chemotherapy. Forty-two patients (77.8%) entered complete remission with 33 (61.0%) remaining in unmaintained remission and 44 (81.5%) alive at a median follow up of 51 months (range: 22-103). The treatment was generally well tolerated with minimal toxicity. ChlVPP is effective first-line treatment for Hodgkin's disease with results which may be comparable to those achieved for MOPP but with significantly less toxicity.
- Published
- 1989
- Full Text
- View/download PDF
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