Biomedical subjects

J A Radford

Publications and source records attributed to J A Radford.

At least 19 recordsLinked to original sources

PubMed2006

Does stretching increase ankle dorsiflexion range of motion? A systematic review.

BACKGROUND: Many lower limb disorders are related to calf muscle tightness and reduced dorsiflexion of the ankle. To treat such disorders, stretches of the calf muscles are commonly prescribed to increase available dorsiflexion of the ankle joint. HYPOTHESIS: To determine the effect of static calf muscle stretching on ankle joint dorsiflexion range of motion. STUDY DESIGN: A systematic review with meta-analyses. METHODS: A systematic review of randomised trials examining static calf muscle stretches compared with no stretching. Trials were identified by searching Cinahl, Embase, Medline, SportDiscus, and Central and by recursive checking of bibliographies. Data were extracted from trial publications, and meta-analyses performed that calculated a weighted mean difference (WMD) for the continuous outcome of ankle dorsiflexion. Sensitivity analyses excluded poorer quality trials. Statistical heterogeneity was assessed using the quantity I2. RESULTS: Five trials met inclusion criteria and reported sufficient data on ankle dorsiflexion to be included in the meta-analyses. The meta-analyses showed that calf muscle stretching increases ankle dorsiflexion after stretching for < or = 15 minutes (WMD 2.07 degrees; 95% confidence interval 0.86 to 3.27), > 15-30 minutes (WMD 3.03 degrees; 95% confidence interval 0.31 to 5.75), and > 30 minutes (WMD 2.49 degrees; 95% confidence interval 0.16 to 4.82). There was a very low to moderate statistical heterogeneity between trials. The meta-analysis results for < or = 15 minutes and > 15-30 minutes of stretching were considered robust when compared with sensitivity analyses that excluded lower quality trials. CONCLUSIONS: Calf muscle stretching provides a small and statistically significant increase in ankle dorsiflexion. However, it is unclear whether the change is clinically important.

Ankle Joint↗

PubMed2006

Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL).

INTRODUCTION: Sequential high dose (SHiDo) chemotherapy with stem cell support has been shown to prolong the event-free survival in patients with diffuse large B-cell lymphoma. METHODS: To confirm this result in a multicenter trial, we randomized patients with aggressive NHL, to receive either eight cycles of CHOP or SHiDo. The primary endpoint was overall survival. RESULTS: 129 evaluable patients were randomized to receive either CHOP or SHiDo: median age, 48 years; 62% male; stage III+IV: 73%; age adjusted International Prognostic Index 1/2/3: 21%/52%/27%. Toxicity grades 3+4 were more pronounced in the SHiDo-arm with 13% versus 3% of patients with fever; 34% versus 13% with infections; 13% versus 2% with esophagitis/dysphagia/gastric ulcer. The remission rates were similar in SHiDo and CHOP arms with 34%/37% complete remissions and 31%/31% partial remissions, respectively. After a median observation time of 48 months, there was no difference in overall survival at 3 years, with 46% for SHiDo and 53% for CHOP (P = 0.48). CONCLUSION: In this multicenter trial, early intensification with SHiDo did not confer any survival benefit in previously untreated patients with aggressive NHL and was associated with a higher incidence of grades 3/4 toxicity.

Adolescent↗

PubMed2006

Response evaluation in gastrointestinal stromal tumours treated with imatinib: misdiagnosis of disease progression on CT due to cystic change in liver metastases.

Imatinib is a highly effective treatment for patients with metastatic gastrointestinal stromal tumours (GIST). In most instances, response to imatinib treatment is assessed with CT. We present two cases where CT demonstrated the appearance of new low density liver lesions after 8-12 weeks of imatinib treatment. While this finding is consistent with progressive disease due to new lesions appearing at a previously uninvolved site, we hypothesise that the appearance of new liver lesions is in fact due to cystic change within previously occult, solid metastases. These untreated solid metastases were not visible on conventional portal phase CT due to their small size and vascular nature. Our hypothesis is supported by the observation that extrahepatic sites of disease had reduced in size over the same period of imatinib treatment and by the subsequent disease outcomes of these two cases. One patient, who continued imatinib because of significant symptomatic improvement despite the CT findings, remained stable on the same dose of imatinib for 18 months. The other patient, whose disease progressed when imatinib was withdrawn, had a dramatic response to treatment when imatinib was restarted at the same dose 2 years later. It is important that radiologists and oncologists who are involved in the management of GIST recognize that the appearance of new, low-density liver lesions on CT may represent a response to treatment. This finding must be correlated with symptomatic response and with tumour sites outside the liver before erroneously withdrawing effective imatinib treatment.

Aged↗

PubMed2004

Tositumomab and iodine I 131 tositumomab for recurrent indolent and transformed B-cell non-Hodgkin's lymphoma.

PURPOSE: An open-label phase II study was conducted at two centers to establish the efficacy and safety of tositumomab and iodine I 131 tositumomab at first or second recurrence of indolent or transformed indolent B-cell lymphoma. PATIENTS AND METHODS: A single dosimetric dose was followed at 7 to 14 days by the patient-specific administered radioactivity required to deliver a total body dose of 0.75 Gy (reduced to 0.65 Gy for patients with platelets counts of 100 to 149 x 10(9)/L). Forty of 41 patients received both infusions. RESULTS: Thirty-one of 41 patients (76%) responded, with 20 patients (49%) achieving either a complete (CR) or unconfirmed complete remission [CR(u)] and 11 patients (27%) achieving a partial remission. Response rates were similar in both indolent (76%) and transformed disease (71%). The overall median duration of remission was 1.3 years. The median duration of remission has not yet been reached for those patients who achieved a CR or CR(u). Eleven patients continue in CR or CR(u) between 2.6+ and 5.2+ years after therapy. Therapy was well tolerated; hematologic toxicity was the principal adverse event. Grade 3 or 4 anemia, neutropenia, and thrombocytopenia were observed in 5%, 45%, and 32% of patients, respectively. Secondary myelodysplasia has occurred in one patient. Four patients developed human antimouse antibodies after therapy. Five of 38 assessable patients have developed an elevated thyroid-stimulating hormone; treatment with thyroxine has been initiated in one patient. CONCLUSION: High overall and CR rates were observed after a single dose of tositumomab and iodine I 131 tositumomab in this patient group. Toxicity was modest and easily managed.

Adult↗

PubMed2004

Limited field radiotherapy for early stage, infra-diaphragmatic Hodgkin's lymphoma.

AIMS: To analyse the treatment outcome for patients with stage I and II infra-diaphragmatic Hodgkin's lymphoma. MATERIALS AND METHODS: A retrospective review of case notes for 33 consecutive patients treated between 1988 and 2000. Twenty-five out of 33 patients received radiotherapy alone, three out of 33 patients received minimal initial chemotherapy (MIT) (4 weeks VAPEC B) and five patients received six cycles of ChlVPP EVA hybrid chemotherapy before radiotherapy. Radiotherapy was given as a limited field in 32 out of 33 patients. RESULTS: Twenty-seven out of 33 patients were men (82%), and the median age was 47 years. Fifteen of the 33 patients were stage IA, 15 were IIA, 1 was IB and 2 were IIB. The median follow-up was 71 months. Histological subtype was lymphocyte predominant (15/33), nodular sclerosis (11/33), mixed cellularity (4/33), lymphocyte-rich classical (1/33) and unclassifiable (2/33). The 5-year overall survival was 89% and 5-year relapse-free survival was 85%. The median time to relapse was 37 months (range 7-65 months). One out of five relapses was within the previous radiotherapy field. All five relapses had received radiotherapy alone and four were salvaged with chemotherapy. There have been four second malignancies and one patient transformed to high-grade non-Hodgkin's lymphoma. No patient has died of Hodgkin's lymphoma. CONCLUSIONS: In our cohort of patients with infra-diaphragmatic stage I and II Hodgkin's lymphoma treated with limited-field radiotherapy, no patients died from uncontrolled disease. The use of MIT may reduce the risk of relapse and obviate the need for conventional salvage chemotherapy. Late relapses may occur, and second malignancies are a cause for concern underlining the need for long-term follow-up.

Adult↗

PubMed2002

Semen cryopreservation, utilisation and reproductive outcome in men treated for Hodgkin's disease.

Between 1978 and 1990, 122 men underwent semen analysis before starting sterilising chemotherapy for Hodgkin's disease. Eighty-one (66%) had semen quality within the normal range, 25 were oligospermic (<20 x 10(6) sperm per ml) and five were azoospermic (no sperm in the ejaculate). Semen from 115 men was cryopreserved and after a median follow-up time of 10.1 years, 33 men have utilised stored semen (actuarial rate 27%) and nine partners have become pregnant resulting in 11 live births and one termination for foetal malformation. Actuarial 10 year rates of destruction of semen before death or utilisation and death before utilisation are 19% and 13% respectively. This retrospective cohort study demonstrates that approximately one-quarter of men utilising cryopreserved semen after treatment for Hodgkin's disease obtain a live birth. The high non-utilisation rate is intriguing and warrants further investigation.

Antineoplastic Agents↗

PubMed2002

ChlVPP/EVA hybrid versus the weekly VAPEC-B regimen for previously untreated Hodgkin's disease.

PURPOSE: To test the hypothesis that a chemotherapy regimen of relatively low toxicity and 11 weeks' duration (doxorubicin, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone [VAPEC-B]) is at least as effective in terms of disease control as 6 months' treatment with chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin (ChlVPP/EVA hybrid), which is associated with a high risk of permanent sterility. PATIENTS AND METHODS: Two hundred eighty-two patients with previously untreated Hodgkin's disease, clinical stages I/II (plus mediastinal bulk and/or B symptoms) and clinical stages III/IV were randomized at three United Kingdom and one Italian center to receive either six monthly cycles of ChlVPP/EVA hybrid or 11 weekly cycles of VAPEC-B. After chemotherapy and a restaging evaluation, radiotherapy was administered to sites of previous bulk or residual radiographic abnormality before patients were observed off treatment. RESULTS: Further accrual to the trial was halted at the planned third interim analysis in September 1996. After a median follow-up of 4.9 years, freedom from progression (FFP), event-free survival (EFS), and overall survival (OS) are all significantly better in the population treated with ChlVPP/EVA than VAPEC-B, where the comparative 5-year results are 82% and 62% (FFP), 78% and 58% (EFS), and 89% and 79% (OS), respectively. The superiority of ChlVPP/EVA was seen in both low-risk and intermediate/high-risk patients, although subset analysis suggested that ChlVPP/EVA and VAPEC-B produce equivalent results in the best-prognosis patients (Hasenclever score <or= 2, nonbulky disease). CONCLUSION: Apart from possibly in the best-prognosis group, where results are equivalent, ChlVPP/EVA hybrid produces significantly better FFP, EFS, and OS than VAPEC-B in patients with previously untreated Hodgkin's disease.

Adolescent↗

PubMed2001

Orthotopic reimplantation of cryopreserved ovarian cortical strips after high-dose chemotherapy for Hodgkin's lymphoma.

BACKGROUND: Infertility is a common late effect of chemotherapy and radiotherapy, and has a substantial effect on the quality of life for young survivors of cancer. For men, semen cryopreservation is a simple way of preserving reproductive potential but for women, storage of mature eggs rarely proves successful, and the alternative-immediate in vitro fertilisation with cryopreservation of embryos-is not always appropriate. Reimplantation of cryopreserved ovarian tissue has been shown to restore natural fertility in animals. We applied this technique in a woman who had received sterilising chemotherapy for lymphoma. METHODS: A 36-year-old woman underwent a right oophorectomy with cryopreservation of ovarian cortical strips before receiving high-dose CBV chemotherapy for a third recurrence of Hodgkin's lymphoma. 19 months later, when serum sex steroid analysis confimed a postmenopausal state, two ovarian cortical strips were thawed and reimplanted-one onto the left ovary and another at the site of the right ovary. FINDINGS: 7 months after reimplantation of ovarian cortical strips, the patient reported resolution of hot flashes and, for the first time, oestradiol was detected in the serum. This finding was associated with a decrease in the concentrations of follicle-stimulating hormone and luteinising hormone, and ultrasonography revealed a 10 mm thick endometrium, a poorly visualised left ovary, and a 2 cm diameter follicular structure to the right of the midline. The patient had one menstrual period, but by 9 months after the implantation, her sex steroid concentrations had returned to those seen with ovarian failure. INTERPRETATION: Orthotopic reimplantation of frozen/thawed ovarian cortical strips is a well tolerated technique for restoring ovarian function in women treated with sterilising chemotherapy for cancer.

Adult↗

PubMed2001

Isolation of germ cells from human testicular tissue for low temperature storage and autotransplantation.

OBJECTIVE: To develop a new protocol for conserving fertile potential in men undergoing sterilizing chemotherapy by low temperature banking of germ cells which can be returned to the patient's testes after thawing. DESIGN: Isolation of human and murine germ cells for comparing cellular viability after cooling to liquid nitrogen temperatures by the use of different cryoprotective agents and for infusion into the testis. SETTING: Laboratory research environment. PATIENT(S): Men undergoing routine surgery in a urology department. INTERVENTION(S): Testicular biopsy. MAIN OUTCOME MEASURE(S): Cellular viability and infusion of seminiferous tubules. RESULT(S): After isolation using a two-step enzymatic disaggregation protocol, 66% to 87% of germ cells from human and murine specimens, respectively, were still viable. Cell survival was similar in four commonly used cryoprotective agents after cooling to liquid nitrogen temperatures. Seminiferous tubules infused by back flow with dye solution via the rete testis were filled with an efficiency of 55%. CONCLUSION(S): Judging from the high viability of unfractionated germ cells, it is feasible to isolate germ cells from testicular biopsies for low temperature banking with the aim of attempting to restore fertility after iatrogenic sterilization.

Animals↗

PubMed2001

Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group.

CAELYX/DOXIL, pegylated liposomal doxorubicin, has shown antitumour activity and reduced toxicity compared with standard doxorubicin in other tumour types. In this prospective randomised trial, 94 eligible patients with advanced soft-tissue sarcoma (STS) were treated, 50 with CAELYX (50 mg/m(2) by a 1 h intravenous (i.v.) infusion every 4 weeks) and 44 with doxorubicin (75 mg/m(2) by an i.v. bolus every 3 weeks). Histological subtypes were evenly matched, 33% were leiomyosarcoma (CAELYX: 18; doxorubicin: 13). Primary disease sites were well matched. CAELYX was significantly less myelosuppressive, only 3 (6%) patients had grade 3 and 4 neutropenia, versus 33 (77%) on doxorubicin; febrile neutropenia occurred in 7 (16%) patients given doxorubicin, but only 1 (2%) given CAELYX. 37 (86%) patients on doxorubicin had grade 2-3 alopecia, but only 3 (6%) on CAELYX, and the major toxicity with CAELYX was to the skin. Palmar-plantar erythrodysesthesia with CAELYX was grade 1: 4 (8%) patients, grade 2: 11 (22%) patients, grade 3: 9 (18%) patients and grade 4: 1 (2%) patient. Other non-haematological grade 3 and 4 toxicities were rare. Confirmed responses were observed with both agents: CAELYX: complete response (CR) 1 (uterine), partial response (PR) 4 (response rate (RR) 10%); and doxorubicin: CR 1, PR 3 (RR of 9%); with the best response being stable disease (NC) in 16 and 18 patients, respectively. The reason for the low response rate is unknown, but it may be due partly to a high proportion of gastrointestinal stromal tumours. In conclusion, CAELYX has equivalent activity to doxorubicin in STS with an improved toxicity profile and should be considered for further investigation in combination with other agents such as ifosfamide.

Adult↗

PubMed2001

Randomized placebo-controlled trial of testosterone replacement in men with mild Leydig cell insufficiency following cytotoxic chemotherapy.

OBJECTIVE: Testosterone deficiency is associated with significant morbidity, and androgen replacement in overt hypogonadism is clearly beneficial. However, there are few data concerning the response to therapy in young men with mild testosterone deficiency. DESIGN AND PATIENTS: We have identified a cohort of 35 men, mean age 40.9 years, with mild Leydig cell dysfunction, defined by a raised LH level (LH >or= 8 IU/l) and a testosterone level in the lower half of the normal range or frankly subnormal (testosterone < 20 nmol/l), following treatment with cytotoxic chemotherapy for malignancy. Patients were assigned randomly to 12 months treatment with transdermal testosterone (n = 16) (Andropatch 2.5 mg patches, 1-2 patches per day) or placebo patches (n = 19) in a single blinded manner. MEASUREMENTS: Measurements of bone mineral density (BMD) and body composition were performed at baseline, 6 months and 12 months using single and dual energy X-ray absorptiometry (SXA, DXA). In addition, spinal BMD was assessed at baseline and 12 months by quantitative CT (QCT). Subjects were reviewed at 3-monthly intervals; at each visit blood was taken for measurement of testosterone, SHBG, LH, FSH, oestradiol, lipids and IGF-1 and patients completed three questionnaires which assessed energy levels, mood and sexual function. RESULTS: Total testosterone and calculated free testosterone increased significantly in the testosterone-treated group compared with the placebo-treated group (13.3 nmol/l and 342.9 pmol/l at baseline compared with 17.3 nmol/l and 454.8 pmol/l during the study period in the testosterone-treated group; P = 0.05 and P = 0.02, respectively). LH was suppressed into the normal range in 15 of the 16 testosterone-treated men and mean LH significantly reduced from 11.1 IU/l at baseline to 6.8 IU/l during the study. There was no significant change in BMD at the hip, spine or forearm and no change in fat or lean body mass. There was a significant reduction in physical fatigue in the testosterone-treated group compared with the placebo-treated group (P = 0.008) and a borderline improvement in activity score (P = 0.05). There were no significant effects of treatment on mood or sexual function. Neither oestradiol nor IGF-1 levels differed between the two groups during the study. There was no significant change in mean total cholesterol, HDL cholesterol or triglyceride levels, but there was a small, but significant reduction in LDL cholesterol levels in the testosterone-treated group compared with the placebo group (P = 0.02). CONCLUSIONS: These results suggest that testosterone therapy in young men with raised LH levels and low/normal testosterone levels does not result in significant changes in BMD, body composition, lipids or quality of life, apart from a reduction in physical fatigue and a small reduction in LDL cholesterol. This implies that mild hypogonadism defined on this basis is not of clinical importance in the majority of men, and that androgen replacement cannot be recommended for routine use in these patients.

Adult↗

PubMed2001

A phase II trial of bryostatin 1 in patients with non-Hodgkin's lymphoma.

Bryostatin 1 is a naturally occurring macrocyclic lactone with promising antitumour and immunomodulatory function in preclinical and phase I clinical investigations. In this phase II study, 17 patients with progressive non-Hodgkin's lymphoma of indolent type (NHL), previously treated with chemotherapy, received a median of 6 (range 1-9) intravenous infusions of 25 microg/m(2) bryostatin 1 given once weekly over 24 hours. In 14 evaluable patients no responses were seen. Stable disease was attained in one patient for 9 months. The principal toxicities were myalgia and phlebitis. Treatment was discontinued early because of toxicity alone (phlebitis) in 2 patients, toxicity in addition to progressive disease in 3 patients (myalgia and phlebitis n = 2; thrombocytopenia n = 1) and progressive disease in 5 patients. The results fail to demonstrate efficacy of this regimen of bryostatin 1 in the treatment of NHL. In light of preclinical data that demonstrate synergy between bryostatin 1 and several cytotoxic agents and cytokines, clinical studies to investigate bryostatin 1 in combination are warranted. We also present data to demonstrate that central venous lines may be used in future studies to avoid phlebitis.

Adult↗

PubMed2000

Effect of high-dose ifosfamide in advanced soft tissue sarcomas. A multicentre phase II study of the EORTC Soft Tissue and Bone Sarcoma Group.

In this phase II study the effect of high-dose ifosfamide (HDI) given as a 3-day continuous infusion at a dose of 12 g/m2 repeated every 4 weeks with adequate mesna protection and hydration was evaluated in patients with advanced soft tissue sarcomas. A total of 124 patients entered the trial of which 10 were ineligible. HDI was given both as first-line and second-line chemotherapy. Median age was 46 years (19-66 years). Median World Health Organization (WHO) performance status was 1 (0-1). Fifty two per cent of the patients were males. The predominant histology was leiomyosarcoma (33%). A maximum of six cycles was given. At the time of analysis 55 patients have died. The partial response (PR) rate was 16%. The median time to progression was 15 weeks. 8 of the 18 responding patients (44%) had synovial sarcomas, whereas only 5% of the patients having leiomyosarcomas responded. The grade 3 + 4 haematological toxicity encountered was neutrophils in 78% and platelets in 12%. The major grade 3 + 4 non-haematological toxicities encountered were febrile neutropenia in 39%, infection in 20%, and acute renal failure in 4%. In conclusion, it is possible to administer HDI on a multicentre basis, but the toxicity is substantial. HDI given as a continuous infusion at this dose cannot be recommended as the standard treatment of advanced soft tissue sarcomas, even in selected patients.

Adult↗

PubMed2000

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↗

PubMed2000

A phase II study to evaluate the combination of fludarabine, mitoxantrone and dexamethasone (FMD) in patients with follicular lymphoma.

BACKGROUND: 'Molecular response' is being investigated as a therapeutic goal in follicular lymphoma (FL). High response rates in FL with the fludarabine combination 'FMD' have been associated with 'molecular remission'. A phase II study of FMD in FL was therefore conducted. PATIENTS AND METHODS: Fifty-four patients, ten of whom were newly diagnosed received FMD. Forty-four percent of the previously treated patients had 'chemoresistant' disease. Treatment comprised: fludarabine 25 mg/m2 days 1-3, mitoxantrone 10 mg/m2 day 1, and dexamethasone 20 mg days 1-5. Blood/bone marrow was collected for quantitation of t(14;18) by 'real-time' PCR. RESULTS: The overall response rate was 37 of 54 (69%), complete responses being seen in 11 patients (20%), with no difference between newly diagnosed and the previously treated patients. However, the response rate in 'chemosensitive' relapse was 84% compared to 44% in patients in whom the last prior regimen had failed. Molecular responses were seen in 17 of 25 and PCR negativity in 8 of 25, although molecular and clinical responses did not always correlate. Toxicity was moderate, 19 patients required admission. However, in 6 of 12 patients, subsequent G-CSF mobilised stem cell harvests failed. CONCLUSIONS: FMD was well tolerated but with a lower than expected response rate. Molecular responses were seen in the majority of responding patients however, 'molecular remission' was rare.

Adult↗

PubMed2000

The impact of mild Leydig cell dysfunction following cytotoxic chemotherapy on bone mineral density (BMD) and body composition.

BACKGROUND: Overt testosterone deficiency is associated with a reduction in BMD and alteration in body composition. However, there are few data concerning the impact of mild hypogonadism on these parameters. PATIENTS AND METHOD: We have identified a cohort of 36 men aged < 55 years with mild Leydig cell impairment, defined by a raised LH level (LH >/= 8 IU/l) in the presence of a testosterone level in the lower half of the normal range or frankly subnormal (< 20 nmol/l), following treatment with procarbazine-containing chemotherapy regimens or high-dose chemotherapy for haematological malignancy. These men underwent measurements of BMD (measured by dual-energy X-ray absorptiometry (DXA), single energy X-ray absorptiometry (SXA) and quantitative CT (QCT)), body composition (DXA), markers of bone turnover, serum lipids and serum IGF-1. To allow for changes that may be directly attributable to the underlying disease or its treatment, results were compared with those obtained in 14 men who had received the same chemotherapy for the same diseases but had normal LH and testosterone levels (controls). RESULTS: When data from all 50 men were considered together there were significant reductions in BMD of the lumbar spine both by DXA (Z = - 0.34, P = 0.01) and QCT (Z = - 1.5, P < 0. 0001), at the femoral neck (Z = - 0.52, P < 0.0001) and distal forearm (Z = - 0.21, P = 0.05). Mean femoral neck BMD was significantly lower in patients compared with controls (Z = - 0.68 vs. Z = - 0.11, P = 0.05) and there was a nonsignificant trend towards lower lumbar spine BMD measured by QCT (Z = - 1.64 vs. Z = - 1.10; P = 0.09). In addition, serum testosterone level and testosterone:LH ratio significantly correlated with femoral neck BMD (r = 0.28, P = 0.05 and r = 0.37, P = 0.008, respectively). There were no significant differences in lean body mass, fat mass and percentage fat between the patients and controls. There was, however, a difference in the distribution of body fat with a propensity for the patients to accrue truncal fat, and the serum testosterone level significantly inversely correlated with percentage of truncal fat (r = - 0.29, P = 0.04). There were no significant differences in lipid levels, IGF-1 levels or markers of bone turnover between the patients and controls. CONCLUSIONS: These data suggest that mild Leydig cell impairment may have significant effects on bone mineral density and may result in subtle body composition changes, although in men who have received cytotoxic chemotherapy, other factors also contribute to the observed osteopenia. Testosterone replacement may be beneficial in some of these men and this requires further evaluation.

Adult↗

PubMed2000

A doxorubicin-based regimen used in the treatment of elderly patients with high-grade non-Hodgkin's lymphoma.

A retrospective analysis was performed on 66 patients, aged 70 years or older, who received treatment with a weekly doxorubicin-containing regimen (VAPEC-B) for high grade non-Hodgkin's lymphoma (NHL). Two dosing schedules were employed. The choice of regimen was at the discretion of the treating clinician and reflected the performance status of the patient and the predicted tolerance to chemotherapy. Forty-nine patients received a half-dose schedule and 17 the full-dose schedule. Those receiving the half-dose regimen had a lower median performance status and received a lower dose intensity of chemotherapy (45% versus 83%). However, the outcomes of the two groups were similar: complete remission rate 41% versus 47%, and 5-year overall survival 36% versus 23%, for the half- and full-dose groups, respectively. A similar proportion of patients (51% versus 59%) completed each regimen, although there were more delays in treatment delivery experienced in those receiving the full dose. Half-dose VAPEC-B is an effective treatment option for elderly patients with high-grade NHL and has comparable efficacy with other published regimens. The use of such low-dose doxorubicin-containing regimens in elderly patients with high-grade NHL requires further investigation.

Aged↗

PubMed2000

Fatigue, sexual function and mood following treatment for haematological malignancy: the impact of mild Leydig cell dysfunction.

Fatigue, sexual dysfunction, anxiety and depression are all more common in patients who have previously been treated with cytotoxic chemotherapy and radiotherapy (XRT) for haematological malignancies. Following therapy, a significant proportion of men have biochemical evidence of Leydig cell dysfunction, defined by a raised luteinizing hormone level in the presence of a low/normal testosterone level. We postulated that mild testosterone deficiency may account for some of the long-term side-effects of treatment, and we have therefore assessed fatigue, mood and sexual function by questionnaire in 36 patients with Leydig cell dysfunction (group 1), and also in a group of 30 patients (group 2) with normal hormone levels who underwent the same treatment for cancer. There was no significant difference in anxiety and depression scores between the two groups although anxiety scores were higher than those previously reported for normal men. Eighty-seven per cent of group 2 were sexually active compared with only 69% of group 1 (P= 0.1), and patients in group 1 engaged less in sexual activity than those in group 2 (mean of 1.8 times per week compared with 3.2 times per week; P = 0.02) Fatigue scores were significantly higher in both groups compared with normal men, but there were no significant differences in any of the fatigue subscales between the two groups. We conclude that mild Leydig cell insufficiency following treatment with cytotoxic chemotherapy +/- XRT is not associated with higher levels of fatigue and anxiety but may result in reduced sexual function. These results do not provide a convincing argument that androgen replacement therapy is mandatory to improve quality of life in the majority of these patients, although it may be beneficial in a minority. To establish criteria for selection of patients for a trial of androgen therapy a randomized placebo-controlled study will be necessary.

Antineoplastic Combined Chemotherapy Protocols↗