Acute leukaemia in the elderly, remission induction versus palliative therapy.
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Biomedical subjects
Publications and source records attributed to G M Mead.
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Fifty-four patients whose disease had been staged as extensive small cell carcinoma of the bronchus were randomised to receive either CAV1 (cyclophosphamide 600 mg m-2 i.v., adriamycin 50 mg m-2 i.v., given on day 1, and etoposide 500 mg m-2 p.o. given on day 3) or CAV5 (cyclophosphamide and adriamycin given as for CAV1, etoposide 500 mg m-2 given in divided dose over days 3-7) on a 21-day schedule. The two regimens proved comparable (CR + PR 55% vs 56%), and the survival curves were virtually superimposable (median survival: CAV1, 8 months; CAV5, 9 months). Only five patients are still alive. The toxicity of the two treatments was similar. The scheduling of etoposide over 1 or 5 days seemed clinically unimportant in this study, perhaps because of concurrent use of other effective chemotherapy drugs.
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A phase II study of tamoxifen was conducted in 22 patients with stage III and IV ovarian cancer who had failed chemotherapy and who had evaluable disease. Tamoxifen was administered at a dose of 20 mg twice daily continuously until evidence of progression. Twenty-one patients had progression of disease within 3 months and one patient had stable disease for 6 months. There were no objective responses to this treatment.
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Thirty-six (10.1 per cent) of a total of 355 adult patients with non-Hodgkin's lymphoma seen over a seven and a half year period developed compression or infiltration of the central nervous system (CNS). In nine patients (2.5 per cent) extradural tumour masses compressed the spinal cord or brain. Five of these patients, all previously untreated, responded well to treatment, with excellent recovery of CNS function and survival in the long term. The prognosis for the four patients with advancing drug-resistant systemic disease at the time of CNS compression was poor. In 27 patients (7.6 per cent) a clinical or cytological diagnosis of meningeal infiltration was made (on cerebrospinal fluid). Meningeal disease was seen most frequently in patients with high-grade lymphoma, either at presentation or during subsequent progression of systemic disease. All of these patients have died of systemic and/or CNS disease less than 20 (median 3) months from diagnosis of meningeal disease. Meningeal infiltration represents a significant clinical problem for which new approaches to prophylaxis and treatment are required.
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Twenty patients with stage III or IV ovarian carcinoma refractory to chlorambucil were treated with IV cisplatin, adriamycin and cyclophosphamide. Two patients achieved CR and four PR, giving an overall response rate of 30%. All patients have since died at 0-18 (median 8) months. Use of this region was associated with marked toxicity, including three drug-related deaths. Second-time drug combinations should be regarded as experimental, and they should probably only be used in selected patients outside of clinical trials.
A randomized study to compare the efficacy of combination chemotherapy (cisplatin, doxorubicin, cyclophosphamide: PACe) with chlorambucil (CB) in International Federation of Gynecology and Obstetrics (FIGO) stage III and IV ovarian carcinoma was conducted between May 1979 and October 1983. Patients failing initial CB were subsequently eligible for treatment with PACe. Eighty-nine patients were randomized and 85 were eligible for analysis; as of date, 72 of these patients have died. The majority of patients in this study had bulky residual disease after their initial laparotomy (76%). Complete response (CR) was documented by a second laparotomy after five cycles of combination therapy or 6 to 12 months alkylating agent therapy. The overall response rate (CR plus partial response [PR]) for the combination (PACe, 68%) was significantly higher (P = .0004) than that for the chlorambucil (CB, 26%). However, the median survival was not improved (PACe, 13 months; CB, 11 months) and the survival curves were not significantly different (log rank test P = .25). The results of this study are comparable to preliminary data reported from other similar randomized studies. PACe, as administered in this study, is not indicated as routine therapy in patients with bulky residual ovarian carcinoma.
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Two cases of Hodgkin's disease are described who relapsed 22 and 19 years after regional radiation therapy. One of the patients also developed a carcinoma of the large bowel soon after first relapse. The importance of long follow-up and documentation of cause of death in Hodgkin's disease is stressed.
Eighty-three patients with histologically proven small cell carcinoma of the lung were entered into a prospective randomised clinical trial to evaluate two induction regimes. A 'low' dose methotrexate regime which employed three cycles of etoposide, adriamycin and methotrexate given at conventional dosage was compared with a regime which employed three cycles of etoposide and adriamycin together with five courses of high dose methotrexate and folinic acid rescue. All patients achieving a complete response (CR) received prophylactic cranial irradiation. Patients with limited disease who achieved a CR received additional radiotherapy to the primary site. An alternative four drug regime (procarbazine, vincristine, cyclophosphamide and CCNU) was evaluated in patients failing to achieve or subsequently relapsing from a complete response. Response rates for the low dose and high dose methotrexate arms were 54 and 55% respectively with median survivals of 8.6 and 9.7 months. Median survival for complete and partial responders was 20.2 and 11 months respectively. The alternative four drug regime showed limited activity in patients failing to achieve a complete response after primary therapy. We conclude that high dose methotrexate as used in this study has no role in small cell lung cancer. The 'low' dose regime was well tolerated by outpatients, is effective and is suitable for generalised use in the palliation of small cell lung cancer.
Case histories from 20 patients undergoing postchemotherapy "second look" laparotomy for metastatic epithelial cell carcinoma of the ovary were reviewed in an attempt to evaluate the usefulness of this procedure and its likely impact on patient survival. The patient population comprised 18 patients treated with a combination of cisplatin, adriamycin and cyclophosphamide (PACe) and 2 patients treated with chlorambucil. The findings at second look were often predictable, and related to the adequacy of initial surgery. Complete tumour regression identified a group of patients with a relatively good prognosis. However in most patients residual tumour was found which rarely proved resectable. Second line chemotherapy was poorly tolerated, and appeared to have little impact on the disease particularly after combination chemotherapy had been used initially. There was little evidence that second look surgery itself positively contributed to survival. This procedure and its timing should be regarded as experimental and a suitable subject for randomised clinical trials.
Thirty-eight patients age 65 years and older with a diagnosis of non-Hodgkin's lymphoma of poor prognostic type were seen over a five and a half year period. These patients represented 19 per cent of our total new patient non-Hodgkin's lymphoma population during this time. Advanced age, coexisting medical illness, widespread lymphoma and poor treatment compliance were common problems. Despite this we were able to render 26 per cent of patients disease-free for periods from 12 to over 48 months. Age should not be considered a bar to staging and effective therapy. Palliative management was unsuccessful, and we believe that treatment should be given with the intention of cure. Features suggesting that a patient was more likely to achieve a lasting complete remission included early stage (I-IIA), a lack of systemic ('B') symptoms, an absence of bone marrow or bulky gastrointestinal tract disease and no pre-existing serious medical condition.
Twelve patients with unfavorable prognosis lymphomas (diffuse histiocytic lymphoma, 11; nodular histiocytic lymphoma, 1) treated predominantly with radiation therapy, are described in whom relapse of disease occurred late (greater than 2.5 years, 2.8-26 years; median, 6.25 years) after achieving a complete remission. Although relapse probably represented regrowth of clinically quiescent tumor, it is also possible that these were second malignancies, perhaps occurring in a predisposed host. Continued long-term analysis of clinical trials is important to document this uncommon occurrence.
From July 1971 to December 1980, 323 cases of non-Hodgkin's lymphoma were randomized into prospective clinical trials at Stanford University Medical Center. Analysis of these cases revealed 30 patients (9.3% of the total) with disease of different histologic subtypes at separate anatomic sites (discordant lymphomas). On further analysis, 16 of these patients (4.8% of the total) were found to have disease of different histological and prognostic types. Recommendation is made that initial therapy be directed at the poor-prognosis component of these tumors. Relapses of both favorable prognostic types and unfavorable histologic types were seen, and further biopsy at the time of relapse is recommended in these cases.
A patient with hairy cell leukaemia is described who developed progressive lymphadenopathy, which proved to be due to Mycobacterium kansasii infection. Clinicians should be alert to this rare but well-described complication of hairy cell leukaemia. Early lymph node biopsy is recommended in patients developing otherwise unexplained fever and lymph node enlargement.