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Biomedical subjects

A Horwich

Publications and source records attributed to A Horwich.

At least 163 records · Page 9Linked to original sources
PubMed1990

Radical radiotherapy for carcinoma of the anal canal.

The treatment of squamous cell carcinoma of the anal canal remains controversial, and recent reports have recommended combined chemotherapy and radiotherapy rather than radiotherapy alone as primary treatment. In order to define the role for more aggressive local therapy we have performed a retrospective analysis on patients with squamous cell carcinoma of the anal canal treated at the Royal Marsden Hospital between 1958 and 1986. Among 42 patients who received radical radiotherapy (RRT) the overall 5-year caused specific survival (CSS) was 52%. Tumour stage and node involvement were the most important prognostic factors. The 5 year CSS were T1 100%, T2 59%, T3 40% and T4 0% (P less than 0.05). The 5-year CSS for node-negative patients was 64% compared to 23% for node-positive patients (P less than 0.095). A minimum tumour dose of 60 Gy in 30 fractions over 6 weeks was essential to achieve local control and was associated with minimal late morbidity and with the retention of anal continence in all patients locally controlled.

Adult↗
PubMed1990

'JEB'--a carboplatin based regimen for malignant germ cell tumours in children.

Between February 1986 and July 1988 a total of 21 children aged 1 to 16 years with malignant germ cell tumours (MGCT), 18 with either metastatic disease or unresectable primary tumour, received the JEB regimen - carboplatin dosage calculated from the EDTA glomerular filtration rate (approximately 600 mg m-2), etoposide 120 mg m-2 daily x 3, and bleomycin 15 mg m-2 weekly. Primary sites were: testis (6), ovary (8), sacrococcyx (4), pineal gland (2) and vagina (1). AFP levels were elevated in 19, beta-HCG in 8. Complete marker response was achieved in 19 out of 19 evaluable patients and complete remission of measurable tumour in 16 out of 19, 12 with chemotherapy alone and 4 with the addition of surgery. A reduction in glomerular filtration rate greater than 10% occurred in 3 of 12 evaluable patients; in none greater than 20%. Sequential audiography was normal in 11 out of 12 evaluated. The regimen was myelosuppressive with WHO grade III or IV myelosuppression occurring in 12 patients. Three patients have relapsed; one with a pineal germinoma who relapsed in the abdomen six months after diagnosis, and two with sacrococcygeal teratomas and lung metastases. Two of these remain in second complete remission after further treatment. There was one death from probable bleomycin pulmonary toxicity. We conclude that this regimen is simple to administer and, apart from myelosuppression, it is well tolerated. It appears to have comparable efficacy to cisplatin-based regimens but with much less nephrotoxicity and ototoxicity and avoids the use of alkylating agents and anthracyclines.

Adolescent↗
PubMed1990

Management of the contralateral testis in patients with testicular germ cell cancer.

Patients with testicular germ cell tumours (TGCT) are at increased risk of developing a tumour in the contralateral testis. Such a tumour may be preceded by carcinoma in situ (CIS), which is more common in patients with infertility, atrophic testis or a history of cryptorchism. Of 1219 patients with TGCT seen at the Royal Marsden Hospital between 1962 and 1984 in whom the contralateral testis was managed by surveillance, 38 (3.1%) developed a second tumour and 8 died of germ cell tumours. Seventeen of 26 assessable patients (65%) exhibited at least one of the known aetiological risk factors for carcinoma in situ. Diagnosis of carcinoma in situ may lead to more appropriate management of the contralateral testis.

Carcinoma in Situ↗
PubMed1990

Persistent carcinoma in situ of the testis after chemotherapy for advanced testicular germ cell tumours.

The chemosensitivity of testicular carcinoma in situ (CIS) was analysed in 25 testes excised 10 weeks to 4.5 years following platinum-based chemotherapy. CIS was present in 8 of the 23 evaluable cases (35%), in 5 of which the lesion coexisted with invasive germ cell tumour. It is concluded that CIS may persist or recur after chemotherapy. This has implications for occult presentation of metastatic germ cell tumours and also for the management of the contralateral testis in patients with testicular germ cell tumours.

Adolescent↗
PubMed1990

Metastatic non-seminomatous germ cell tumour and dermatomyositis.

Twenty to thirty percent of cases of dermatomyositis in adults are associated with malignancy. We report a case in which dermatomyositis heralded the development of a testicular germ cell tumour. Germ cell testicular tumours are treatable and our case emphasizes the importance of measuring blood levels of beta-human chorionic gonadotrophin and alpha-fetoprotein and examination of the testes in young males with indications of possible malignancy.

Adult↗
PubMed1989

Carboplatin and etoposide pharmacokinetics in patients with testicular teratoma.

The pharmacokinetics of carboplatin and etoposide were studied in four testicular teratoma patients receiving four courses each of combination chemotherapy consisting of etoposide (120 mg/m2 daily x 3); bleomycin (30 mg weekly) and carboplatin. The carboplatin dose was calculated so as to achieve a constant area under the plasma concentration vs time curve (AUC) of 4.5 mg carboplatin/ml x min by using the formula: dose = 4.5 x (GFR + 25), where GFR is the absolute glomerular filtration rate measured by 51Cr-EDTA clearance. Carboplatin was given on either day 1 or day 2 of each course and pharmacokinetic studies were carried out in each patient on two courses. Etoposide pharmacokinetics were also studied on two separate courses in each patient on the day on which carboplatin was given and on a day when etoposide was given alone. The pharmacokinetics of carboplatin were the same on both the first and second courses, on which studies were carried out with overall mean +/- SD values (n = 8) of 4.8 +/- 0.6 mg/ml x min, 94 +/- 21 min, 129 +/- 21 min, 20.1 +/- 5.41, 155 +/- 33 ml/min and 102 +/- 24 ml/min for the AUC, beta-phase half-life (t 1/2 beta), mean residence time (MRT), volume of distribution (Vd) and total body (TCLR) and renal clearances (RCLR), respectively. The renal clearance of carboplatin was not significantly different from the GFR (132 +/- 32 ml/min). Etoposide pharmacokinetics were also the same on the two courses studied, with overall mean values +/- SD (n = 8) of: AUC = 5.1 +/- 0.9 mg/ml x min, t 1/2 alpha = 40 +/- 9 min, t 1/2 beta = 257 +/- 21 min, MRT = 292 +/- 25 min, Vd = 13.3 +/- 1.31, TCLR = 46 +/- 9 ml/min and RCLR = 17.6 +/- 6.3 ml/min when the drug was given alone and AUC = 5.3 +/- 0.6 mg/ml x min, t 1/2 alpha = 34 +/- 6 min, t 1/2 beta = 242 +/- 25 min, MRT = 292 +/- 25 min, Vd = 12.5 +/- 1.81, TCLR = 43 +/- 6 ml/min and RCLR = 13.4 +/- 3.5 ml/min when it was given in combination with carboplatin. Thus, the equation used to determine the carboplatin accurately predicted the AUC observed and the pharmacokinetics of etoposide were not altered by concurrent carboplatin administration. The therapeutic efficacy and toxicity of the carboplatin-etoposide-bleomycin combination will be compared to those of cisplatin, etoposide and bleomycin in a randomised trial.

Antineoplastic Agents↗
PubMed1989

Stage III Hodgkin's disease--long-term results following chemotherapy, radiotherapy and combined modality therapy.

215 patients with stage III Hodgkin's disease (HD) were treated at the Royal Marsden Hospital between 1963 and 1985 (median follow-up 9 years). The actuarial 5- and 10-year survival was 77 and 65%, respectively with 55 and 48% 5 and 10 year disease-free survival. Of 13 variables tested, age was the only independent prognostic indicator for survival on multivariate analysis. Patients aged under 40, 40-59 and over 60 years had a 10-year survival of 76, 41 and 8%, respectively (p much less than 0.001). Ninety-one patients were initially treated with combined chemotherapy and radiotherapy (combined modality therapy, CMT), 73 patients with radiotherapy (RT) and 51 patients with chemotherapy (CT) alone. Patients under 40 years treated with CMT achieved the best disease-free survival (10 year disease-free survival: CMT 68%; RT 38%; CT 45%). The observed survival advantage for CMT was not statistically significant. In patients aged greater than 40 there was no survival or disease-free survival advantage following CMT. Analysis of recurrence pattern confirmed that CMT improves initial disease control both at previously involved and uninvolved sites. Recurrences at previously uninvolved sites continued up to 6 years following CT, up to 8 years following CMT and up to 14 years after RT alone. These results indicate that only long-term follow-up gives the true picture of stage III HD.

Adolescent↗
PubMed1989

Intensive induction chemotherapy for poor risk non-seminomatous germ cell tumours.

An increase in initial chemotherapy intensity was evaluated in 29 patients with high risk metastatic non-seminomatous germ cell tumours (NSGCT) of the testis, defined by the presence of multiple large lung metastases, liver, bone or brain metastases, or the combination of large abdominal mass with high serum concentration of the tumour markers alpha-foetoprotein (AFP) or beta subunit of human chorionic gonadotrophin (HCG) (AFP greater than 500 ku/l or HCG greater than 1000 iu/l). Four courses of bleomycin, vincristine and cisplatin (BOP) were given at 7 day intervals, followed by three courses of etoposide, cisplatin with or without bleomycin (BEP or EP) at 21 day intervals for a total of 13 weeks of chemotherapy. Twenty-three (85%) of 27 evaluable patients have remained continuously free from disease progression at a median of 24 months (range 14-38 months) from chemotherapy and the actuarial 2 year freedom from progression rate is 86% (95% CI = 73-99%). Three patients died from non-malignant causes, two of bleomycin pneumonitis and one from complications of cystic fibrosis. Thus cause specific overall survival in the total population of treated patients is 79%. With appropriate limitation of bleomycin dosage, this approach is well tolerated and results compare favourably with less intensive induction schedules based on initial 21-28 day cycles.

Adolescent↗
PubMed1989

The late effects of cis-platinum on renal function.

The combination of bleomycin, etoposide and cis-platinum (BEP) is an effective treatment for germ cell tumours. To help define the role of recently developed non-nephrotoxic analogues of cis-platinum we have analysed the long term renal damage caused by this agent. We report on 22 patients studied 8-60 months following BEP chemotherapy. In the 17 cases with no pre-chemotherapy renal impairment there was a fall in mean glomerular filtration rate from 132 ml/min (95% confidence interval 123, 141) pre-chemotherapy to 103 ml/min (95% confidence interval 94, 113) on late follow up. The overall pattern is one of initial fall of glomerular filtration rate during chemotherapy, and no consistent evidence of late recovery or further deterioration; considerable individual variation is observed.

Adolescent↗
PubMed1989

The management of paratesticular rhabdomyosarcoma.

Between 1974 and 1986 15 patients presented to the Royal Marsden Hospital with paratesticular rhabdomysarcoma. Of 10 patients presenting with Stage I disease, eight were treated with adjuvant chemotherapy. Six (75%) remain continuously disease-free 1.2-8.3 years from presentation. The two who relapsed have been salvaged with further treatment and remain disease-free 7.5 years and 10.3 years from original presentation. Three patients presented with regional node involvement and two are disease-free 3.3 and 3.7 years from presentation; the other died from disease. Two patients presented with Stage III disease and one remains alive and disease-free at 7.8 years from presentation. The efficacy of chemotherapy has diminished the roles of surgery and radiotherapy following radical excision in Stage I disease. However, aggressive multi-modality approaches are relevant for metastatic disease.

Adolescent↗
PubMed1989

Changing patterns of relapse in Hodgkin's disease.

The patterns of early and late relapses (those occurring later than 3 years after diagnosis) in 432 patients achieving complete remission after treatment for stage I and II Hodgkin's disease at the Royal Marsden Hospital between 1964 and 1983 were studied to identify factors predicting for late relapse. The incidence of early relapse has fallen progressively in recent treatment eras as staging procedures and management have improved but in contrast there has been no decrease in the risk of late relapse. The incidence of late relapse was greater in patients treated with radiotherapy rather than combined modality therapy (P less than 0.05). However, patients who were clinically staged and treated with combined modality therapy retained as high a risk of relapse between 3 and 6 years as in years 2 and 3. The risk of late relapse was also greater in patients with stage II disease and in those without B symptoms at presentation. Patients falling into the higher risk categories for late relapse require continued close follow-up beyond 3 years to monitor for possible relapse.

Adolescent↗
PubMed1989

Technetium-99m HMPAO and SPECT in the assessment of blood flow in human lung tumours.

In order to assess the blood flow patterns through human lung tumours, 20 patients received 400-750 MBq 99TcmHMPAO intravenously 10 min before single photon emission computed tomography (SPECT). Ratios of uptake in the whole tumour relative to normal lung ranged from 0.35 to 1.53 (mean 1.01) with eight tumours showing less uptake than normal lung and ten showing greater uptake. In one patient the tumour was not distinguishable from surrounding lung and in another a large pleural effusion prevented evaluation. Tumour: lung ratios for central tumour regions ranged from 0 to 1.83 (mean 0.80) with 13 showing lower uptake than normal lung and five showing greater uptake. Duplicate scans were performed in eight patients demonstrating satisfactory reproducibility. This technique provides a simple and reproducible method for the assessment of tumour blood flow.

Adult↗