Adjuvant interferon alpha 2b in high risk melanoma - the Scottish study.

In 1989, the Scottish melanoma group initiated a randomized trial, comparing observation alone with 6 months' therapy with low dose interferon (given subcutaneously 3 MU day-1, twice weekly), for patients with primary melanomas of at least 3 mm Breslow thickness, or with evidence of regional node involvement. The trial was closed in 1993 with only 95 eligible patients randomized. There were no toxic deaths, and no patient failed to complete the treatment for reasons of toxicity. 6 months' treatment with low-dose interferon- resulted in a statistically significant improved disease-free survival for up to 24 months after randomization (P< 0.05). However, at a median follow-up of over 6 years, although there was an apparent improvement in disease-free survival (from 9 to 22 months), and overall survival (from 27 to 39 months), consistent with larger studies powered to detect such differences, these differences were not statistically significant. The data therefore suggest that 6 months of low-dose interferon is active, and confirm the importance of the large randomized studies, such as the UKCCCR AIM-High and EORTC trials, that seek to confirm a possible survival advantage for low or intermediate dose interferon.

Encounters with doctors: quantity and quality.

Continuity of care and the large numbers of health care professionals who deliver that care are issues that frequently concern patients and their families. This study examined the number of doctors encountered by 50 patients, during the period of their cancer care. This ranged from 4 months to 26 years, with a median time of 2 years and 4 months. The doctors included in this number were general practitioners, doctors met during hospital inpatient admissions and when attending outpatient appointments, and doctors at the hospice. Descriptive statistics are included detailing the total number of doctors encountered by patients; the number met by patients within the first year of their cancer care; and the average number of new doctors met each year. The minimum number of doctors met was 13, maximum 97 and median 32. Notable examples include one patient who met 31 doctors during a 6-month period, and one patient who met 73 doctors during a period of 2 years and 1 month. Patients in this study with a history of less than 1 year met 28 doctors on average. Semi-structured interviews with these patients were conducted adopting a qualitative approach. Patients were asked about their recollections of the doctors they had met during their cancer care and what value they attributed to these encounters. Interviews were subject to thematic analysis. The major themes to emerge were: continuity of care, the provision of information and explanations and honesty in that process, breaking of bad news, the manner adopted by the doctor and issues relating to specialist referral. The large number of health care professionals, including the doctors quantified in this study, involved in the care of each patient represents a major challenge to 'seamless' and consistent communication between those involved.

Screening for psychiatric illness in the palliative care inpatient setting: a comparison between the Hospital Anxiety and Depression Scale and the General Health Questionnaire-12.

The objective of this study was to compare the performance of the Hospital Anxiety and Depression Scale (HADS) with the 12-item General Health Questionnaire (GHQ-12) as a screening instrument for the detection of psychiatric disorders in a palliative care inpatient setting. The results from the HADS and GHQ were compared to diagnoses generated from a semistructured psychiatric interview (Revised Clinical Interview Schedule) using standard receiver operating characteristic analysis. The study was conducted at the Marie Curie Centre, Edinburgh, a 37-bedded palliative care inpatient facility. Out of a total of 282 admissions during the study period, 79 took part in the study. The remainder of patients either refused (69) or were too unwell to participate (134). The HADS was found to be an effective screening tool for identifying depression, with an area under the receiver operating characteristic curve of 0.92. A suggested cut-off of 20 would have a sensitivity of 0.77, a specificity of 0.85 and a positive predictive value (PPV) of 0.48. There was no significant difference between the two subscales in their ability to detect depressive illnesses, although there was a trend for the anxiety subscale to perform better (P < 0.15). The GHQ did not perform as well as the HADS in this type of population. In view of this, it can be concluded that the HADS is a valid screening tool for psychiatric disorders, particularly depression, in a palliative care setting.

Radiotherapy for stages I and II testicular seminoma: results and morbidity in 238 patients.

We have undertaken a retrospective analysis of 238 patients with Stages I and II seminoma of the testis treated with radiotherapy in Edinburgh between 1974 and 1989. There were five deaths from seminoma. Cause-specific survival for the whole group at 2 and 5 years was 99.2% and 98.1%, respectively. Cause-specific survival at 2 and 5 years by stage (Royal Marsden staging classification) was: Stage I, 99.5% and 98.7% and Stage II, 98.1% and 96.1%. Fourteen (5.9%) patients relapsed (one after treatment for his second testicular seminoma). Eight were given successful salvage treatment, five died of seminoma and one died of intercurrent disease. 13 (5.5%) patients developed World Health Organisation (WHO) grade 3 gastrointestinal or haematological toxicity and two developed grade 4 gastrointestinal toxicity as a result of abdominal radiotherapy. 22 patients (9.2%) developed problems ascribed to late morbidity of abdominal radiotherapy including 18 with peptic ulcer disease. Contralateral testicular tumours occurred in seven (2.9%) patients and five (2.1%) patients developed malignancies at other sites.

Information giving in oncology: a preliminary study of tape-recorder use.

This paper describes a pilot study of information giving in an oncology setting. This was achieved by randomly allocating patients to having their consultation tape-recorded or not. The results suggest that this approach increases the retention of information in patients as well as reducing their levels of anxiety. The method is cheap and easy to use, acceptable to patients and their families, and does not inhibit the consultation process.

A phase I and pharmacology study of GR63178A, a water-soluble analogue of mitoquidone.

GR63178A is a water-soluble analogue of mitoquidone, a pentacyclic pyrroloquinone. This group of drugs exhibit a novel structure and activity against several murine solid tumours and xenografts. In the present phase I study the toxicity and pharmacokinetics of GR63178A given on 5 consecutive days of a 21-day cycle were examined. A total of 24 patients presenting with a wide range of tumours were treated at 5 doses escalated to reach the maximal tolerated dose (MTD). Linear pharmacokinetics was documented over the dose range studied, and there was no difference in parent drug handling between day 1 and day 4 of dosing. A number of metabolites were detected. The toxicity profile was unusual in that pain occurred in 20/24 patients, most often at the site of known disease. This was the dose-limiting toxicity. Other side effects included nausea and vomiting (23/24), phlebitis at the infusion site (6/24) and headache (7/24). No treatment response was seen in this study. The MTD was demonstrated to be 160 mg/m2 daily (total, 800 mg/m2 per treatment cycle). The drug has now entered phase II trials at 120 mg/m2 daily x 5, repeated every 21 days.

Does dexamethasone enhance control of acute cisplatin induced emesis by ondansetron?

OBJECTIVE: To determine the contribution of dexamethasone to the efficacy of the 5-hydroxytryptamine antagonist ondansetron in control of cisplatin induced nausea and vomiting. DESIGN: Randomised double blind crossover study. SETTING: Two cancer centres in teaching hospitals, one in the United Kingdom and the other in Germany. SUBJECTS: 100 patients (53 men and 47 women) new to cisplatin chemotherapy, 84 of whom completed two consecutive courses of chemotherapy. INTERVENTIONS: Patients were given intravenous dexamethasone (20 mg) or physiological saline with intravenous ondansetron 8 mg before cisplatin, then ondansetron 1 mg/h for 24 hours. Oral ondansetron 8 mg was taken three times daily on days 2-6. MAIN OUTCOME MEASURES: Incidence of complete or major control of emesis (0-2 episodes in the 24 hours after chemotherapy). RESULTS: Complete or major control was obtained in 49 out of 71 (69%) of patients after receiving ondansetron plus dexamethasone compared with 40 out of 71 (56%) when they were given ondansetron alone (p = 0.012). This effect was most pronounced in the first 12 hours after chemotherapy. Patients receiving the combination also had significantly less nausea. Of the 53 patients who expressed a preference, 38 (72%) preferred the combination treatment (p = 0.002) to ondansetron alone. The effect of ondansetron on delayed emesis was less pronounced. CONCLUSIONS: Dexamethasone makes a significant contribution to the efficacy of ondansetron in the control of acute platinum induced emesis.

Mucinous endometrial carcinoma in a patient with previous ovarian endometrioid adenocarcinoma presenting some 18 years after initial bilateral ovariectomy: a case report.

The association of endometrioid carcinoma of the ovary and primary carcinoma of the endometrium is well recognised. These tumours are often synchronous in occurrence. Oestrogen stimulation is often postulated as a significant factor in the development of the endometrial carcinoma in such cases. We describe the case of a patient who developed a mucinous endometrial carcinoma 18 years after initial bilateral ovariectomy. The aetiology and pathogenesis of the uterine tumour is discussed.

Neoadjuvant chemotherapy with methotrexate and cisplatin prior to radiotherapy for invasive transitional cell carcinoma of the bladder. Assessment of feasibility and toxicity.

A prospective study has been performed to assess the feasibility and toxicity of administering neoadjuvant chemotherapy with methotrexate (200 mg/m2) and cisplatin (100 mg/m2) prior to radical radiotherapy. Twenty patients with advanced transitional cell carcinoma of the bladder were assessed after each of 3 courses of chemotherapy, after radiotherapy and 6 months following treatment. Of particular concern was whether neoadjuvant chemotherapy compromised the ability to give potentially curative radical radiotherapy, delayed effective palliation of distressing urinary symptoms, or allowed local tumour progression prior to definitive treatment. It was concluded that this chemotherapy regimen was well tolerated, did not compromise the ability to give radical radiotherapy and resulted in the prompt palliation of urinary symptoms. This treatment, however, did not stop the development or progression of metastatic disease in some patients. In only 1 patient was there local progression during chemotherapy.

Surgery following chemotherapy for metastatic testicular teratoma.

Twenty patients with metastatic testicular teratoma underwent surgery for residual disease after chemotherapy. Twelve patients in whom complete excision of all residual masses was possible are alive with no evidence of disease. Four patients have died of malignant teratoma, 2 have active malignant disease and 2 have inoperable residual cystic disease. Patients with malignant teratoma intermediate (MTI) primary testis tumours, and those with bulky abdominal disease at presentation, are more likely to have residual masses requiring excision. Completeness of excision appears to be the most important predictor of disease-free survival.

Low dose bleomycin with etoposide and cisplatin for metastatic testicular teratoma.

Thirty-nine men with metastatic testicular teratoma were treated with a combination of bleomycin, etoposide and cisplatin (BEP). Unlike the usual regimen of these 3 agents, bleomycin and cisplatin were given on day 1 only of the cycle, with etoposide for 3 days. Thirty patients (77%) are alive and disease-free after a median follow-up of 31 months--24/25 (96%) with disease confined to lymph nodes but only 6/14 (43%) patients with lung involvement. Modified BEP chemotherapy is a well tolerated alternative to standard BEP chemotherapy for small volume nodal disease; it minimises in-patient time, hospital visits and the risk of bleomycin lung toxicity. However, omission of the weekly doses of bleomycin and shortening of the administration schedule of cisplatin and etoposide may be detrimental in patients with more extensive disease, for whom more intensive therapy may be necessary.

Failure of salvage treatment in metastatic testicular teratoma.

From January 1978 to March 1989, 92 consecutive patients with metastatic testicular teratoma have been treated with cisplatin-based chemotherapy. Thirty seven failed to achieve a complete response, and another four subsequently relapsed. These 41 have required further treatment, consisting of surgery (16 patients), radiotherapy (n = 13) and chemotherapy (n = 12). Surgery was generally used for residual masses where tumour markers were normal, radiotherapy for masses where surgery was not possible or for palliation, and second line chemotherapy was used in patients with raised serum tumour markers or in the presence of multiple inoperable pulmonary metastases. Nine of 16 (56%) patients treated surgically are disease-free, including two who had malignant teratoma in the resection specimen. Three of 13 patients irradiated are disease-free, although two of these three had subsequent excision of residual masses. All 12 patients treated with second-line chemotherapy have died. Surgical excision of residual masses appears to be the most effective way of rendering patients disease-free, providing serum tumour markers are normal. Most of these residual masses will consist of differentiated teratoma or necrosis, but it may be possible to salvage patients with residual malignant disease, providing complete clearance can be achieved. Incompletely resected malignant disease carries a poor prognosis, and incompletely resected disease that is histologically benign will run the risk of subsequent relapse. Radiotherapy provides good palliation but is much less effective than surgery as treatment for residual masses, and should only be used if complete excision cannot be accomplished.(ABSTRACT TRUNCATED AT 250 WORDS)

Potentiation of cisplatin by alpha-interferon in advanced non-small cell lung cancer (NSCLC): a phase II study.

Studies in experimental human lung cancer models have suggested that interferon may enhance significantly the response to some cytotoxic drugs. We have performed a phase II study of cisplatin (100 mg/m2 q.21 or 28 days) and alpha-2 interferon (3 or 5 MU three times weekly) in 68 patients with advanced non-small cell lung cancer and good performance status. As toxicity was acceptable, the dose of interferon and schedule of cisplatin were increased at the midpoint of the study. 46% (11/24) of patients with squamous carcinoma responded and an overall partial response rate of 30% was attained in 60 evaluable patients. There was no potentiation of haematological, renal or neurological toxicity but nausea and vomiting were severe. These results suggest that the combination has activity in this usually refractory disease.