Etoposide and adriamycin containing combination chemotherapy (HOPE-Bleo) for relapsed Hodgkin's disease.

Forty-four patients with relapsed or resistant Hodgkin's disease were treated with adriamycin 40 mg m-2 i.v. on day 1, vincristine 1.4 mg m-2 i.v. on days 1 and 8, prednisolone 40 mg m-2 orally daily for 8 days, etoposide 200 mg m-2 orally daily for 4 days according to the nadir white cell count, and bleomycin 10 mg m-2 i.v. days 1 and 8 (HOPE-Bleo). Median age was 27 (range 12-71). When stage was considered according to all sites currently or previously involved by Hodgkin's disease (cumulative stage) 26 patients (59%) had stage IV, 13 (29%) stage III and five (11%) stage II disease; 33 (75%) had B symptoms. All patients had received previous chemotherapy and 18 (41%) had received two or more regimens. Twenty-six patients (59%) achieved CR and 10 (23%) PR; the median duration of CR was 22 months and median survival for all patients was 48 months. Eight patients remain in continuous CR; none of these had received extensive previous chemotherapy. Among the 19 patients who had relapsed from CR achieved by a single previous chemotherapy regimen, six (32%) achieved long CR on HOPE-Bleo. The regimen was generally well tolerated but the principal toxicity was myelosuppression. There were two toxic deaths, one due to neutropenic sepsis and the other due to acute peritonitis. The HOPE-Bleo regimen is an effective treatment for relapsed or resistant Hodgkin's disease, with a low probability of carcinogenesis and infertility. These factors suggest that HOPE-Bleo deserves further evaluation as primary treatment for Hodgkin's disease and very careful selection of relapsed patients for high dose salvage chemotherapy with bone marrow transplants must be exercised

High dose melphalan, BCNU and etoposide with autologous bone marrow transplantation for Hodgkin's disease.

Thirty-eight patients with previously treated Hodgkin's disease were given high dose combination chemotherapy using melphalan and BCNU and autologous bone marrow transplantation. In 25 patients etoposide was added in conventional dosage. During the course of the study the dose of melphalan was increased from 80 to 140 mg m-2 and the dose of BCNU from 300 to 600 mg m-2. The response rate was 76% with 53% complete remission. Forty-five per cent of the patients are free of disease at 4-20 months follow-up. There were eight (26%) treatment-related deaths due to lung damage (seven cases) and irreversible cardiac failure (one case). Fatal lung damage occurred only in patients receiving 600 mg m-2 of BCNU with high dose melphalan. The dose of BCNU given with high dose melphalan should not exceed 500 mg m-2. This treatment is effective against relapsed Hodgkin's disease but must be used cautiously. The best time for its use remains to be determined

The value of computed tomographic (CT) scan surveillance in the detection and management of brain metastases in patients with small cell lung cancer.

One hundred and twenty-seven consecutive patients presenting with small cell lung cancer were entered into a whole-brain CT scan surveillance study, starting at presentation and repeating at 3-monthly intervals for 2 years as an alternative to prophylactic cranial irradiation (PCI). The aim of the study was to detect CNS metastases at an early asymptomatic stage in the hope that prompt CNS radiotherapy could achieve long-term control; at the same time unnecessary PCI with its potential long-term morbidity could be avoided. CNS metastases were found in 56 patients (44%) including 16 (13%) at diagnosis and 40 at a median of 4 months (range 1-27 months) after completing chemotherapy. No patient developed CNS disease while on chemotherapy. Thirty-six patients were asymptomatic at diagnosis (group A) but 20 developed clinical CNS relapse between scans (group B) (interval relapse). Despite prompt radiotherapy 56% of patients in group A and 60% of patients in group B died with active CNS disease. Likewise, there was no survival difference between patients in group A, group B or those who never developed CNS disease. Regular 3-month CT scan surveillance is therefore not an effective substitute for PCI

The use of tumour markers CEA, CA-195 and CA-242 in evaluating the response to chemotherapy in patients with advanced colorectal cancer.

Tumour markers CEA, CA-195 and CA-242 were measured in 33 patients undergoing chemotherapy for advanced colorectal cancer. The aim was to determine whether they could be used to accurately monitor the course of the disease, and reduce the need for imaging. Treatment with a 5-fluorouracil based regimen resulted in a partial response in nine patients (27%), whereas the remainder either had disease stabilisation or suffered from progression. Before treatment the CEA was elevated in 85% of patients and the CA-195 and CA-242 in 78%. All three markers were elevated in 70% and at least one elevated in 93%. CA-195 and CA-242 appeared to be co-expressed, by contrast with the CEA. When compared to the results of serial CT scanning the CEA correlated best with the course of the disease, the positive predictive value being 54% for a partial response, 77% for minor and partial responses combined and 100% for progressive disease. The corresponding values for CA-195 were 46%, 62% and 100% respectively and for CA-242, 50%, 67% and 100% respectively. Thus, although falling levels of markers overestimate the number of responses demonstrated by imaging, rising tumour markers invariably herald progressive disease. This was often evident up to 16 weeks before progression was observed on scanning. CEA is the most useful of the three markers in the monitoring of patients being treated for advanced colorectal cancer, but other markers may prove valuable if the CEA is normal. The use of tumour markers should reduce the need for regular scanning

High dose BCNU chemotherapy with autologous bone marrow transplantation and full dose radiotherapy for grade IV astrocytoma.

In a series of 22 patients, high dose BCNU (800-1,000mg m-2) with autologous bone marrow transplantation was given as the first post-surgical treatment for grade IV astrocytoma and followed by full dose radiotherapy. When compared to historical experience and matched to control patients in national studies, there appeared to be a small prolongation of survival but no increase in the proportion of long survivors. Acute myelosuppression was mild but toxicity to lung and liver was substantial and limited further dose escalation. Late bone marrow failure was seen in 4 patients. Pharmacokinetic studies were performed and suggested that the late marrow failure was due to persistence of BCNU at the time of marrow return. Despite the suggestion of a prolongation of survival this approach is not routinely recommended and a randomised trial is probably not justified

'I just want a job' : what do we really know about young people in jobs without training?

Over recent years, a central concern of policy has been to drive up post-16 participation rates in full-time education and address the needs of young people not in education, employment or training (NEET). As a result, young people who enter work which is classified as 'without training' at 16/17 have largely been ignored. However, the decision to Raise the Participation Age (RPA) for continuing in learning for all 17-year olds from 2013 and for all 18-year olds from 2015 in England, together with a growing unease about the impact of the current recession on youth unemployment rates, have revived interest in the 'jobs without training' (JWT) group. This paper draws on the findings from two studies: first, a qualitative study in two contrasting local labour markets, of young people in JWT, together with their employers and parents; and second, an evaluation of the Learning Agreement Pilots (LAP), which was the first policy initiative in England targeted at the JWT group. Both studies reveal a dearth of understanding about early labour market entrants and a lack of policy intervention and infrastructure to support the needs of the JWT group throughout the UK. From this, it is concluded that questionable assumptions have been made about the composition and the aspirations of young people in JWT, and their employers, on the basis of little or no evidence. As a consequence, a policy 'quick fix' to satisfy the RPA agenda will not easily be achieved. If the decision to raise the participation age is adopted also by the Welsh and Scottish parliaments, similar challenges may have to be faced

Phase II study of docetaxel in combination with epirubicin and protracted venous infusion 5-fluorouracil (ETF) in patients with recurrent or metastatic breast cancer. A Yorkshire breast cancer research group study

This study was originally designed as a phase I/II study, with a dose escalation of docetaxel in combination with epirubicin 50 mg m⁻² and 5-fluorouracil (5-FU) 200 mg m⁻² day⁻¹. However, as dose escalation was not possible, the study is reported as a phase II study of the combination to assess response and toxicity. A total of 51 patients with locally advanced or metastatic breast cancer were treated on this phase II study, with doses of docetaxel 50 mg m⁻², epirubicin 50 mg m⁻² and infusional 5-FU 200 mg m⁻² day⁻¹ for 21 days. The main toxicity of this combination was neutropenia with 89% of patients having grade 3 and 4 neutropenia, and 39% of patients experiencing febrile neutropenia. Nonhaematological toxicity was mild. The overall response rate in the assessable patients was 64%, with median progression-free survival of 38 weeks, and median survival of 70 weeks. The ETF regimen was found to be toxic, and it was not possible to escalate the dose of docetaxel above the first dose level. This regimen has therefore not been taken any further, but as a development of this a new study is ongoing, combining 3-weekly epirubicin, weekly docetaxel and capecitabine, days 1-14