Biomedical subjects
Publications and source records attributed to S Ahmedzai.
Palliative (terminal) care is now recognized worldwide as an important, multidisciplinary aspect of the continuing care of patients with incurable cancer. Symptom control and quality-of-life are of the essence. Various treatment methods are available, and radiotherapy and chemotherapy (used appropriately) are important modalities. Palliative care has to be set against a background of planning, development, and cost-benefit analyses.
OBJECTIVE: To obtain baseline information about hospice clinical activity. DESIGN: Survey of hospices by postal questionnaire and telephone interview. SETTING: 98 Hospices in the United Kingdom and Republic of Ireland of 111 that had a named matron or senior nurse, including 17 funded by NHS and 81 independent units. PARTICIPANTS: Hospice matrons or nursing sisters in charge, to whom the questionnaire was addressed. RESULTS: Median age of hospices was 7 years, and those built during the past seven years had a median of 12 inpatient beds. All NHS hospices had some input from a medical consultant whereas 12 (15%) of independent units did not. 72 Hospices had home care teams and 12 of 20 of these randomly contacted by telephone provided 24 hour cover. The median number of whole time equivalent nurses was four, but 6 (30%) of teams did not include a doctor. Wide variations were found in discharge rates (range 1-76%) and throughput (1.7-31.8 patients/bed/year). In units with a full time consultant or medical director throughput was greater and more patients had palliative surgery and became organ donors than in units without (45/48 v 38/50 and 45/48 v 25/50, respectively). With the exception of pulmonary function tests and insertion of nasogastric tubes and indwelling epidural catheters, tests and procedures were used by over 90% of hospices, although sometimes the patient had to be transferred elsewhere. CONCLUSIONS: Respondents from units with a full time consultant or medical director were more likely to choose a "technical" description of their unit, such as "a pain relief centre" than those without, who favoured non-technical descriptions. These differences are likely to increase with the appointment of more fully trained consultants in palliative medicine.
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Hospice care has developed along different paths in Europe, North America, and other cultures. Even within Britain, there is a diversity of hospice models--in-patient units, hospital support teams, day care and home care, with a broad range of clinical services offered. In assessing the clinical results of a hospice service, it is important to bear these differences in mind. Now that more formal, experimental controlled research is being conducted in hospices, there is an opportunity to evaluate quality of life in the same way that has become accepted in clinical cancer trials. The range of evaluations is reviewed, from purely physical assessment to psychological, social, and spiritual problems and the monitoring of bereavement. It is clear that new measurement instruments are needed, particularly for the social and spiritual problems of hospice patients and their families.
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Ninety five patients (57 with limited disease and 38 with extensive disease) with previously untreated small cell lung cancer were entered into a study of short duration combination chemotherapy with intravenous cyclophosphamide (750 mg/m2) on day 1, adriamycin (40 mg/m2) on day 1, and etoposide VP-16 (100 mg/m2) on days 1, 2, and 3, with the addition on day 10 of methotrexate 50 mg/m2 with folinic acid rescue and vincristine 2 mg. The treatment was repeated on day 22 and only three courses were given. No maintenance chemotherapy was given, though patients with a complete response received radiotherapy (30-40 Gy (3000-4000 rads] to the primary site in most cases. Forty nine patients (86%) with limited disease achieved a response, with 26 (46%) complete remissions. Twenty five patients (66%) with extensive disease had a response, but only eight (21%) had a complete response. Actuarial survival analysis for the whole patient population showed a median survival of 13 months for patients with limited disease and seven months for those with extensive disease. The median survival was 14 months for those patients with limited disease who achieved a complete response, but only 10 months for non-responders. Myelosuppression was the major expression of toxicity. There were three deaths related to treatment and seven patients had febrile episodes during neutropenia that required antibiotics. Mucositis, which was usually mild, occurred in 49% of patients. The primary site was the main site of initial relapse in 56% of the patients who relapsed. Among patients with limited disease who achieved a complete response, relapses at the primary site were less common in those who received radiotherapy (five out of 12) than in those who did not (all eight). The results indicate that this short duration chemotherapy in small cell lung cancer gives response rates and the potential for long term survival similar to those obtained in other series while allowing patients the maximum time free from treatment.
This study investigated the use of late dose intensification therapy (LDIT) with cyclophosphamide (180 mg/kg) and VP 16 (1 g/m2) plus autologous bone marrow rescue in 22 patients with small cell lung cancer (SCLC). These patients were selected from a group of 95 patients who received three courses of a five-drug induction regimen comprising cyclophosphamide (750-1000 mg/m2), adriamycin (40 mg/m2), VP 16 (100 mg/m2) for 3 days, methotrexate (50 mg/m2) and vincristine (2 mg) (CAVMO). There were 16 patients with limited disease, 8 of whom were in complete remission (CR) and 8 in partial remission (PR) after the induction therapy. The other 6 patients had extensive disease; 3 of these achieved CR and 3 PR after induction therapy. Of the 11 patients in PR, 5 responded to LDIT; 3 had a further PR, and 2 CR. Subsequent to LDIT radiotherapy 4000 cGy was given to the primary site in 10 of the 22 patients. Since the start of the study, 19 of the 22 patients have relapsed and died (median survival 11 months), while 3 remain alive and in remission at 11, 11, and 24 months. Comparison of the survival of patients receiving LDIT with that of an equivalent group (with respect to staging and response to induction chemotherapy) of patients who received induction chemotherapy alone showed no significant difference. In this study, LDIT following conventional induction therapy in patients with chemosensitive tumours did not improve survival.
Reviews of published studies indicate that the incorporation of VP-16 (Vepesid) into combination chemotherapy for small-cell lung cancer may improve overall response rates from 50% to between 65% and 80%. In addition, high-dose VP-16 may yield a higher response rate than that obtained with conventional doses. The West of Scotland Lung Cancer Group has therefore conducted studies to examine the effects of VP-16 both in a combination regimen as induction therapy and (together with high-dose cyclophosphamide) as late intensification therapy in high dose, aimed at preventing relapse in responding patients. Response to induction treatment improved with the addition of VP-16, compared to earlier studies carried out by the group, yielding an overall response rate of 80% for patients with limited disease and 62% for those with extensive disease. Although induction therapy comprised only three courses (lasting 9 weeks), the median response duration of 9.5 months for complete responders and the median survival of 14 months for complete responders (limited disease) were in keeping with those obtained using more prolonged induction therapy. The intensification therapy with high-dose cyclophosphamide and high-dose VP-16, however, yielded no improvement in overall survival in those responding patients who received it compared with those who did not. Radiotherapy following late-dose intensification prevented local tumor recurrence but appeared to have no effect on overall survival. Resistance to VP-16 and other drugs is a possible deterrent to successful therapy in small-cell lung cancer, and it is suggested that research focus on a possible role for calcium channel blockers in circumventing drug resistance.
One hundred and five patients with inoperable non-small cell lung cancer were included in a randomized trial comparing the activity of vindesine as a single agent with the combination of vindesine and cisplatin. All patients were previously untreated and the majority (70%) had squamous carcinoma. The overall partial response rates in 88 evaluable patients were 7% for vindesine alone and 33% for the combined regime. There were no complete responders in either arm. The median survival of patients treated with vindesine and cisplatin was 11 months, compared with 4 months in those treated with vindesine alone (P = 0.008). Patients showing a partial or complete response to vindesine and cisplatin survived a median duration of 13 months, compared with 7 months for non-responders (P = 0.03). This survival benefit associated with the combination was particularly apparent for patients with ECOG performance status 0 or 1 (median survival greater than 18 months and 13 months respectively), locoregional disease (median survival 14 months) and squamous cell histology (median survival 13 months). Myelo-suppression was greater with the combination but was not a major treatment problem. Neurotoxicity, which was frequently dose-limiting, was of similar severity in both treatment groups. The results indicate that the combination of vindesine and cisplatin is superior to vindesine alone for remission induction in non-small cell lung cancer and confers a significant survival advantage compared with vindesine alone in patients with favourable prognostic factors.
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Nabilone, a synthetic cannabinoid, and Prochlorperazine were compared in a double-blind crossover study of 34 patients with lung cancer undergoing a 3-day schedule of chemotherapy with Cyclophosphamide, Adriamycin and Etoposide. Symptom scores were significantly better for patients on nabilone for nausea, retching and vomiting (P less than 0.05). Fewer subjects vomited with nabilone (P = 0.05) and the number of vomiting episodes was lower (P less than 0.05); no patients on nabilone required additional parenteral anti-emetic. More patients preferred nabilone for anti-emetic control (P less than 0.005). Adverse effects common with nabilone were drowsiness (57%), postural dizziness (35%) and lightheadedness (18%). Euphoria was seen in 14% and a "high" in 7%. Erect systolic blood pressure was lower in nabilone patients on Day 1 (P = 0.05) but postural hypotension was a major problem in only 7%. Nabilone is an effective oral anti-emetic drug for moderately toxic chemotherapy, but the range and unpredictability of its side-effects warrant caution in its use.
A survey of residents' (junior house officers') experiences and attitudes to the terminal care part of their work in four Glasgow teaching hospitals showed that even a month after starting work one-fifth of the respondents had not actively managed a dying patient. Sixty-four per cent thought that they had received inadequate teaching in terminal care. Depression and anxiety had been the most difficult symptoms encountered. The residents thought that the ward nursing staff contributed much more than their senior medical colleagues to both the medical and psychological aspects of terminal care. The results indicate a need for more undergraduate education in the most relevant areas, such as coping with the psychological problems of dying patients and their relatives. Newly qualified residents require more support from senior medical staff in looking after the terminally ill.
During the last few years several factors have contributed to an increasing change in the medical treatment of advanced colorectal cancer. Among them are the more general acceptance of the impact of chemotherapy on quality of life and survival in first as well as in second-line treatment, the introduction of new drugs and the definition of novel endpoints which can roughly be defined as "patient benefit". For this reason the European Organization for Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Cooperative Group (GITCCG) felt it was appropriate to organize a workshop with experts from different countries and national groups to discuss in depth several aspects concerning the treatment of patients with advanced colorectal cancer.