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Kaposi's sarcoma is currently the most common tumor in Zimbabwe. The purpose of our study is to compare the effectiveness of supportive care vs. 3 intervention approaches, namely oral Etoposide, a 3-drug combination, and radiotherapy using quality of life (QOL) as the primary measure of success. In addition, our study was to determine whether a disease-specific module has greater sensitivity to group differences than a generic QOL questionnaire and to determine the most pragmatic approach to treating epidemic Kaposi's sarcoma (EKS) in Zimbabwe. Histologically confirmed HIV-positive patients with Kaposi's sarcoma were randomized to receive supportive care only or supportive care plus either radiotherapy, oral Etoposide or a 3-drug combination consisting of actinomycin-D, vincristine and bleomycin. No patient received antiretroviral therapy. The primary outcome was QOL measured by the functional living index-cancer (FLI-C) and supplemented by the Kaposi's sarcoma module (KSM). From 1994-1999, 495 EKS patients were accrued, and 470 were evaluable. Of these, 433 are known to be dead, 26 are lost to follow-up and 11 are still alive. The group treated with oral Etoposide had a significantly better QOL than the radiotherapy group for the total FLI-C score (adjusted mean plus standard error at 3-months 89 +/- 3 vs. 76 +/- 3; p = 0.004) and for the hardship (11 +/- 0.4 vs. 9 +/- 0.4; p = 0.001); social (10 +/- 0.4 vs. 8 +/- 0.4; p = 0.001) and nausea (9 +/- 0.4 vs. 8 +/- 0.4; p = 0.002) subscales. In addition, on the physical and psychological subscales, the Etoposide group had a significantly better QOL than the other 3 treatment groups (p < 0.04). The 3-drug combination, supportive care and radiotherapy groups did not differ significantly from each other with respect to the total FLI-C score or its subscales. There were no group differences with respect to survival. Oral Etoposide therapy resulted in better total FLI-C QOL score than radiotherapy. As well, Etoposide resulted in better physical and psychological subscale scores than radiotherapy, 3-drugs and supportive care. Thus, funds permitting, oral Etoposide is a pragmatic approach to treating EKS in an environment where antiretroviral drugs are not universally available. The study underscores the value of undertaking studies in areas of disease prevalence and the necessity of selecting appropriate outcome measures.

Quality-of-life assessment has become an accepted method of evaluation in clinical medicine. The technique is based on a patient's self-assessment of physical, psychological, and social function, as well as the effects of distressing physical symptoms. The most important aspect of quality-of-life assessment is that it brings into focus a patient-centred view of health outcome, which is broader than the physiologic measures which predominate in Western medicine. Strategies for the development and use of assessment questionnaires have evolved over the past 15 years, and numerous questionnaires have been created. Most originate in Western societies, with English as the most common language of development. Adapting such questionnaires for use in other language and cultural settings is an imprecise practice. Language translation and equivalent cultural meaning must both be addressed. This paper reports on the language translation process and results for the Functional Living Index for Cancer (FLIC) as translated into Chinese and Malay in Singapore. We employed a step-wise process beginning with translation/back translation, followed by structured pilot field trials and population sampling. Taped versions of the questionnaire were devised to meet illiteracy problems in the sample population. Paired comparisons of the Chinese and Malay versions of individual questions with their English counterparts show good correlations and similar means most of the time. Factor analysis on a population sample of 246 (112 Chinese, 35 Malay and 98 English speaking) with cancers of minimal, extensive or palliative extent is convergent with that obtained on a North American population. However, a separate analysis of the Chinese questionnaires showed some differences in factor pattern. Specific language and cultural translation difficulties are discussed. Of note is the predicted significant decrease in total FLIC scores with extent of disease within each of the language preference populations, which provides some evidence for the validity for each language version in the Singapore culture(s). Thus, the FLIC translations into Malay and Chinese in Singapore can be considered for use in local trials, subject to ongoing evaluation.

To assess the long-term effects of cancer treatment and consequences of cure, 102 index cancer cases were compared with 95 neighbourhood controls of similar age and sex and with 78 cardiac controls. The quality of life experienced by these three groups was examined using multiple instruments with proven psychometric properties. All the major quality of life domains (physical, psychological and social) were covered. The findings revealed that the index cases were similar to their neighbours in areas of subjective well-being. However, the index cases exhibited more sexual dysfunction, were more conscientious, determined and emotionally disciplined, and applied the defence mechanisms of displacement and reaction formation more often than the neighbourhood controls. The cardiac controls were older, more anxious, more conventional/less imaginative and used suppression as a defence mechanism to a greater degree than the index cases. In conclusion, young adult cancer survivors enjoy a quality of life similar to their neighbours, whereas coronary bypass survivors adjust less well psychosocially.

A programme of repeated high dose chemotherapy for advanced breast cancer was developed using (1) cyclophosphamide 4 g/m2 followed by autologous peripheral blood stem cell (PBSC) collection; (2) three cycles of conventional dose chemotherapy; (3) high dose cyclophosphamide, cisplatin, and carmustine with PBSC rescue; and (4) high dose etoposide and melphalan with PBSC rescue. Fifteen eligible patients had advanced poor prognosis breast cancer either at initial diagnosis (one patient) or at relapse (14 patients). During the course of the protocol, there were three treatment related deaths, two patient withdrawals due to debilitating toxicity, five patient withdrawals due to disease progression, and one patient withdrawal due to inadequate collection of PBSC. The remaining four patients did not complete the planned protocol as the programme was terminated because of the unacceptable morbidity and mortality. They were treated with an alternative high dose chemotherapy protocol which was well tolerated. This study highlights the significant problems associated with a complex sequential high dose chemotherapy regimen. Cyclophosphamide mobilized PBSC infused following high dose chemotherapy enables rapid haematological recovery. However the non-haematological toxicity following high dose chemotherapy regimens is often severe and may limit the application of certain sequential high dose chemotherapy combinations in patients with breast cancer.

Primary central nervous system (CNS) lymphoma appears to be on the increase. This increase is real rather than due to changes in nosology, physician awareness or increase in high-risk groups. Diagnostic guidelines appear to be well defined and widely accepted. We report 9 cases of primary CNS lymphoma seen at our institution over a 5-year period. The clinical presentation was variable, but consisted mostly of headache, motor dysfunction, and memory and behavioural disturbance. Surgery is of value for diagnosis. In general, surgical decompression is not recommended. Glucocorticoids and radiotherapy appear effective in the short term. The role of chemotherapy is uncertain.

The disposition of unchanged cisplatin was compared after two- and 24-hour intravenous (IV) infusion to eight patients with germ cell cancer (dose, 100 mg/m2), 14 patients with head and neck cancer (dose, seven patients 50 mg/m2; seven patients, 100 mg/m2). Patients were randomized to receive either a two- or 24-hour infusion in the first course of treatment and the reverse in the second course. Cisplatin renal clearance, total clearance, and the percentage of the dose excreted unchanged in urine were significantly lower with the longer infusion. Total clearance was 345 +/- 97.0 mL/min/m2 after the two-hour infusion and 268 +/- 70.7 mL/min/m2 after the 24-hour infusion (P less than .0001). Renal clearance was 79.1 +/- 35.3 mL/min/m2 and 34.1 +/- 14.9 mL/min/m2 (P less than .0001). The percentage of the dose excreted unchanged in urine was 22.9 +/- 6.5% and 12.8 +/- 4.0%, respectively (P less than .0001). The ratio of cisplatin renal clearance to creatinine clearance was 1.95 +/- .96 after the two-hour infusion and .90 +/- .40 after the 24-hour infusion (P less than .001). There was only a poor relationship between cisplatin renal clearance and creatinine clearance after a two-hour infusion (r2 = .05, P greater than .1) or 24-hour infusion (r2 = .18, P greater than .05). The severity of emesis was graded on a four-point scale and was significantly less with the 24-hour infusion than with the two-hour infusion (P less than .05). Twenty-four-hour infusion of cisplatin resulted in greater drug retention in patients due to reduced renal clearance, but was also associated with reduced emetic toxicity, probably as a result of lower peak plasma levels.

We studied 19 Ugandan boys with Hodgkin's disease who had been treated with mechlorethamine, vincristine, procarbazine and prednisone and who survived at least two years to assess testicular germ-cell depletion in pubescent boys on combination chemotherapy, as had previously been demonstrated in sexually mature men. Nine of 13 pubertal boys (ages 11 to 16) had moderate to severe gynecomastia and germinal aplasia, a 10-fold increase in mean (+/- S.D.) serum follicle-stimulating hormone (34.8 +/- 20.5 mlU per milliliter), a threefold increase in mean luteinizing hormone (17.8 +/- 9.8 mlU per milliliter) and reduced serum testosterone levels. Gynecomastia was not associated with an increase in either serum estradiol or prolactin concentrations. By contrast, six prepubertal boys (three to 10 years of age), similarly treated, showed no change in serum gonadotropins, and gynecomastia did not develop. The data confirm germ-cell depletion after combination chemotherapy and indicate further that Leydig-cell dysfunction, manifested by gynecomastia, may be a consequence of treatment in adolescent boys.

47 patients with histologically proven Kaposi's sarcoma were treated with multiple courses of Rezoxane (each course: 1 g/m2/day for 3 days) orally. The overall response was 57% with 20% achieving complete response. The median remission duration of the complete responders is 12 months (range 2--26) with 6 still having sustained complete remissions. Most of the responders were patients with nodular mixed type of Kaposi's sarcoma. The toxicity was minimal and was mainly leukopenia, alopecia and gastrointestinal disturbance. Rezoxane is a useful safe drug and easy to administer to patients with Kaposi's sarcoma.

In a Phase II clinical trial, 14 patients with histologically proven primary hepatocellular carcinoma were treated with adriamycin administered intravenously at a dose of 75 mg/m2 every 3 weeks. All 11 evaluable patients responded with 3 exhibiting complete tumor regression after two, three, and five courses of adriamycin respectively. The remission durations for these 3 were 3, 6, and 7 months, and their survivals were 8, 9, and 13 months, respectively. The median survival of the evaluable patients is 8 months (range 1-13 months). The side effects encountered included myelosuppression, anorexia, nausea, vomiting, and alopecia. Adriamycin seems to be an effective agent in hepatocellular carcinoma. Further trials are underway to test its true efficacy both singly and in combination with other drugs in the management of this tumor.

Twelve cases of childhood Kaposi's sarcoma seen at the Uganda Cancer Institute over the last 7 years are reported. The disease presents mainly as generalized lymphadenopathy, with sparsely and anomalously distributed cutaneous nodules, and has a higher proportion of females with the disease than in the adult form. The histology is usually of mixed cell type. If not treated, childhood Kaposi's sarcoma runs a fulminating course, but disease control with chemotherapy is associated with prolonged survival.

The important factors in the causation of hepatocellular carcinoma (HCC) in Africa include hepatitis B virus (HBV), aflatoxin and possibly malnutrition. The evidence in support of an association of HBV with HCC is mainly epidemiological and includes: (a) the similarity between the geographical distribution of chronic carriers of hepatitis B surface antigen (HBsAg) and that of HCC; (b) the increased prevalence of HBV markers in the serum of patients with HCC when compared with the general population; and (c) the observation that HBV infection precedes the general development of the tumour and that HBV infection increases the risk of HCC over 200-fold. Laboratory evidence has shown that HBV DNA is integrated in the host tissue in patients with HCC. A vaccination programme in Senegal showed that hepatitis B vaccine reduced HBV infection and it is hoped that it will eventually lead to a reduction in HCC. Studies in East Africa have shown a correlation between aflatoxin contamination and the incidence of HCC. The possible roles of malnutrition and/or alcohol are discussed.

Specific biochemical molecules used as potential biologic markers, including modified nucleosides, polyamines, and pyrimidine catabolic end-products, were quantitatively measured in the urine of seven patients with Burkitt's lymphoma before, during, and after one or more courses of therapy. The results of this preliminary study demonstrated that patients with this disease frequently excrete significantly increased amounts oof modified nuceleosides (considered to be derived primarily from transfer ribonucleic acid), polyamines, and beta-aminoisobutyric acid during the course of their disease. With successful treatment and rapid destruction of tumor cells, a concomitant rise in these molecules occurs. Elevations were observed prior to chemotherapy and changes in levels associated with treatment or tumor progression appeared to correlate with disease status and to aid in assessing antitumor response. Periodic follow-up analysis of these molecules may be helfful in appraising relapse or recurrence of the malignancy prior to overt evidence of tumor by existing clincial means.

Fifty-six adult patients diagnosed as having 'cerebral malaria' were admitted and treated over a 4 month period. The presenting symptoms were similar to those of control patients with malaria without cerebral manifestations except that vomiting and convulsions were significantly more frequent and joint pains were less frequent in the cases than in the controls. Physical examination revealed significantly more frequent occurrence of nuchal rigidity, positive Kernig's sign, confusion, muteness, pallor and jaundice in the cases than controls, while splenomegaly was significantly more common in controls than cases. Laboratory data showed that cerebral malaria cases had significantly lower haemoglobin and significantly higher reticulocyte count and erythrocyte sedimentation rate than controls. There was no significant difference in the parasite density between the cases and controls. All patients were treated with 200 mg base of intravenous chloroquine in 250 ml of isotonic saline infused over 2 h and repeated 12 hourly till oral therapy was possible. This proved to be efficacious and the recovery rate was over 90%. Five patients died and the diagnosis was confirmed in three in whom autopsy was permitted. A simple staging system is proposed which retrospectively seems to have prognostic value. It is recommended that the validity of this system be tested prospectively.

The cumulative results and long-term follow-up of all patients with Burkitt's lymphoma treated at the Uganda cancer Institute Kampala are reported. The annual admission rate is 29. The tumor patients commonly present with jaw swelling (72%), abdominal swelling (56%) and central nervous system involvement (30%). Complete response rate is achieved in a high proportion of patients (81%). About 50% of these relapse, equal numbers relapsing before and after 3 months. The most important factor influencing remission duration and survival is disease stage. Other important factors are treatment protocols and, to a lesser extent, the type of relapse. Central nervous system relapse does not necessarily augur poor prognosis as second remissions and long-term survival can be achieved with appropriate therapy. Presently 25% of all treated patients have survived free of disease well beyond 5 years.

Twenty-two patients with Burkitt's lymphoma in complete remission induced by either cyclophosphamide or a combination of cyclophosphamide, oncovin and methotrexate were randomized to receive or not to receive prophylactic cerebrospinal irradiation. Six of 11 irradiated patients relapsed with tumour of the central nervous system as compared to 4 of 11 controls. Relapse frequency appeared to be related to stage of disease on admission. It is concluded that irradiation does not prevent relapse.

Hypercalcemia is a common cause of morbidity in cancer patients. The mechanism of malignancy-associated hypercalcemia includes increased bone resorption and decreased renal calcium clearance which also occur in primary hyperparathyroidism. Norethisterone can inhibit bone resorption and has recently been shown to be effective treatment for mild hyperparathyroidism in post menopausal women. We report the successful use for the first time of norethisterone (5 mg daily) in a case of malignancy-associated hypercalcemia after other standard agents failed.

The exact etiology of Kaposi's sarcoma (KS) remains unknown. Certain observed features suggest a possible viral etiology, including: (a) the spontaneous regression of indolent forms; (b) the frequent occurrence of second primary malignancies; (c) the multifocal nature of KS. Electron microscopic studies have revealed herpesvirus-type particles which morphologically resemble cytomegalovirus (CMV). Sera from KS patients in Europe and America have higher anti-CMV antibodies than controls, in contrast to African patients, whose CMV antibody titres are not significantly different from those of controls. This difference may be related to the high background of CMV antibody in the general African population. Nucleic acid hybridization studies have revealed CMV DNA in some African KS tissue. The possible role of human T-cell leukaemia/lymphoma virus (HTLV) in the causation of KS is discussed in the light of recent evidence of its association with acquired immunodeficiency syndrome (AIDS). Similarly, the possible predisposing role of HLA-DR5 in patients with AIDS and KS is considered.

Burkitt's lymphoma (BL) has been widely investigated and has attracted attention because of the possible etiologic role of the Epstein-Barr virus (EBV). To further determine the role of EBV in the causation of this tumor, we measured EBV-specific nuclear antigen (EBNA) and EBV DNA using immunofluorescence and nucleic acid hybridization techniques, respectively. Of 34 BL biopsies, 27 tissues (79%) were EBNA-positive, whereas none of the 25 non-BL biopsy tissues were EBNA-positive. Of 15 BL tumors tested, 14 (93%) were EBV DNA-positive with a mean of 39 (range, 8-86) EBV genome equivalents per cell. Each of the 15 non-BL biopsy specimens subjected to nucleic acid hybridization had less than two virus genome equivalents per cell, although all had serologic evidence of past EBV infection. The findings further supported the possible etiologic role of EBV in African BL and negated the passenger hypothesis. The EBV genome could, therefore, be used as a separating marker between African BL and non-BL lymphomas.

Although Burkitt's lymphoma (BL) can be treated by surgery, radiotherapy and immunotherapy, chemotherapy is the mainstay of treatment. This paper summarizes the various clinical trials undertaken in Africa over the past decade. The single most effective drug for BL is cyclophosphamide (CPM). Given alone for remission induction, CPM is as effective as combinations consisting of either CPM, vincristine (VCR) and methotrexate (MTX) or CPM, VCR and cytosine arabinoside (Ara-C). Survival data indicate that single-dose CPM is comparable to multiple doses. Thus, maintenance therapy may not be necessary, and may in fact worsen the final outcome. Intrathecal (IT) MTX given together with systemic therapy significantly delays central nervous system (CNS) relapse, which is not prevented by cerebrospinal irradiation. For established CNS disease, IT-Ara-C for three days followed by MTX on the fourth day is effective. Bacillus Calmette-Guérin scarification, while provoking measurable responses in vivo and in vitro, had no measurable, specific anti-tumour reaction, since no effect was observed on relapse rate, duration of remission or survival. High-dose CPM produces objective responses in patients previously resistant to conventional doses. Teniposide (VM 26) is currently undergoing phase 2 trial, and definite short-lived responses have been recorded.

192 Ugandan patients with Burkitt's lymphoma were treated with various regimens containing high-dose cyclophosphamide. 21 patients died during induction therapy, and 14 died after partial responses. Of 157 patients who responded completely to treatment, 16 were lost to follow-up (10 in 69 died and 72 (51%) are alive and disease-free. 31 of the long-term survivors have relapsed at least once and have been successfully retreated. Overall, 34 surviving patients had central-nervous-system involvement, also successfully treated. It is concluded that Burkitt's lymphoma is curable in at least 50% of patients, and that relapse and central-nervous-system involvement are not incompatible with long survival.

Bleomycin either alone or in combination with radiotherapy was used in the treatment of 24 patients with non-resectable cancer of the oesophagus. Improvement in performance (swallowing) status was observed in 75% of patients, although only 19% were known to be alive after 1 year of follow-up. Patients with liver cancer were treated with adriamycin. The response rate was dose dependent and was 40% at best. Combination of adriamycin with other drugs did not improve the response rate. Intra-arterial adriamycin appears more efficacious and gave a response rate of 60%.

There is a considerable volume of evidence linking Epstein-Barr virus (EBV) etiologically with Burkitt's lymphoma (BL). BL has satisfied the Henle-Koch criteria. Thus BL patients have significantly higher EBV antibody titres than normal or tumour controls. EBV DNA and EBV-determined nuclear antigen (EBNA) have been demonstrated in a high proportion (greater than 90%) of endemic BL tissues. EBV can transform and immortalize human B-lymphocytes and is known to cause lymphoreticular tumours in New World monkeys. The fact that endemic BL is almost invariably associated with EBV while this is rarely true of the non-endemic form suggests disease heterogeneity in spite of morphological uniformity. The role of malaria as a co-factor in causing immunosuppression and promoting proliferation of EBV-transformed cell is discussed. The identification of specific chromosomal abnormalities in both endemic and non-endemic BL underscores the importance of a suitable genetic background.

One hundred and thirty nine patients with histologically proven hepatocellular carcinoma (HC) were admitted to the Uganda Cancer Institute for treatment. The patients were considerably younger and seemed to have more advanced disease than HC patients in Europe and in North America. Of the 99 evaluable patients, 50 received Adriamycin intravenously; of these, 44% responded, with 10% achieving complete responses. Intraarterial Adriamycin tended to increase the response rate to 75%, but this may be merely a reflection of patient selection. Combination of Adriamycin with other drugs (dichloromethotrexate, 5-azacytidine, Rezoxane and cyclophosphamide) did not enhance its therapeutic effectiveness. The alphafetoprotein response curves observed when Adriamycin was combined with dichloromethotrexate suggested possible antagonisms between the two drugs. Hepatic artery ligation (HAL) is a good and simple palliative procedure with response rates similar to i.v. Adriamycin. However, the administration of Adriamycin after HAL tended to improve on response rates and survival. The toxicities observed were mainly myelosuppression, gastrointestinal disturbance, alopecia, and hyperpigmentation of the skin and mucous membranes.