Epstein-Barr virus-associated and other antiviral antibodies during intense BCG administration to patients with Burkitt's lymphoma in remission.

Patients with Burkitt's lymphoma in chemotherapy-induced remission received through dermal scarifications one or two doses per week of approximately 3 X 10(8) living BCG organisms (Pasteur Institute vaccine). This treatment was always followed by usually rapid increases by 1--4 log2 steps in the antibody titers to Epstein-Barr virus (EBV)-associated cell membrane antigens. Titer increases of less than 2.5 log2 steps within the first month after the start of BCG treatment correlated with a significantly elevated frequency of extradural relapse as compared to that seen in patients with larger titer rises. During this time, antibodies to EBV-associated viral capsid antigens and early antigens of D and R specificity, as well as antibodies against herpes simplex, varicella, cytomegalovirus, measles, and respiratory syncytial virus antigens, did not show any consistent or impressive changes.

Epstein-Barr virus genome studies in Burkitt's and non-Burkitt's lymphomas in Uganda.

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.

A clinical trial of chemotherapy and RAJI immunotherapy in advanced acute lymphatic leukemia.

Patients in remission with advanced acute lymphatic leukemia were randomly assigned to receive chemotherapy alone or chemotherapy plus immunotherapy with a Burkitt lymphoma tissue culture cell line (RAJI). Remission duration in both groups were identical. Complement-dependent cytotoxic antibody was seen in 5 of 8 immunized patients and 0 of 8 controls. This antibody reacted with RAJI and both allogeneic and autologous acute leukemia cells. Antibody titers began to rise after 2 months, peaked at 4 months, and then declined prior to relapse in all patients. The time course of the increase in mixed-leukocyte culture response to RAJI was similar to immunized patients. An increased in vitro response to phytohemagglutinin was seen during drug administration in all patients. Although no clinical benefit was seen in this small number of patients with the RAJI injections, these in vitro responses are encouraging and new immunization schedules will be investigated.

Patterns of treatment failure and prognostic factors associated with the treatment of esophageal carcinoma with chemotherapy and radiotherapy either as sole treatment or followed by surgery .

PURPOSE: The records of patients with esophageal cancer who were treated with a combined modality therapy were reviewed to determine the effects of simultaneously administered chemotherapy and radiotherapy (RT) at sites of recurrence and the relationship between treatment outcome and clinicopathologic variables. PATIENTS AND METHODS: One hundred seventeen patients were treated with fluorouracil (800 mg/m2) [corrected] and cisplatin (80 mg/m2) combined with either 36 Gy (36 patients) or 54 to 60 Gy (35 patients) of RT as sole therapy. Forty-six patients underwent surgery after they had received chemotherapy and 36 Gy of RT as initial treatment. Patients with either squamous cell cancer (SCC) or adenocarcinoma were included. RESULTS: Complete endoscopic regression after an initial 36 Gy of RT and chemotherapy occurred in more than 50% of patients and in both tumor types. Relief of dysphagia accompanied tumor regression. Forty-two tumors were resected, and 11 showed a complete histologic response. Significant associations were demonstrated between enhanced survival and a diagnosis of SCC, a complete endoscopic response to initial chemotherapy and RT, and a tumor length of less than 5 cm. Multivariate analyses suggested that tumor length and complete endoscopic response were independent prognostic variables. The survival rate of patients treated by resection or radical-dosage RT was not significantly different. CONCLUSIONS: The relief of dysphagia demonstrates the palliative value of chemotherapy and RT in both tumor types. The similar survival rates of patients with SCC or adenocarcinoma treated either surgically or with high-dose combined therapy (54 to 60 Gy) emphasize the need to evaluate the role of surgery and combined treatment in randomized studies.

Two- versus 24-hour infusion of cisplatin: pharmacokinetic considerations.

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.

Long-term effects of cancer treatment and consequences of cure: cancer survivors enjoy quality of life similar to their neighbours.

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.

Plasma concentrations and renal clearance of morphine, morphine-3-glucuronide and morphine-6-glucuronide in cancer patients receiving morphine.

The plasma concentrations and renal clearance values of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were determined in 11 adult cancer patients maintained on a long term oral morphine dosage (10 to 100mg every 4h). Concentrations in plasma and urine were determined by a specific high performance liquid chromatography assay. In this group of patients, whose creatinine clearance values ranged from 52 to 180 ml/min (3.12 to 10.8 L/h), average steady-state plasma concentrations of morphine, M3G and M6G were related (p < 0.01) to the morphine dose per kilogram of bodyweight. The mean total urinary recovery as morphine, M3G and M6G was 74.6 +/- 26.5% of the dose. Renal clearance values for M3G and M6G were closely related (r2 = 0.80; p < 0.0005). It was not possible to detect a relationship between the renal clearance of morphine, M3G and M6G, and that of creatinine. The renal tubular handling of all 3 compounds showed wide interindividual variation, and there was evidence of either net renal tubular secretion or reabsorption. There was no apparent relationship between plasma morphine and M6G concentrations and pain relief.

Non-haematological toxicity limiting the application of sequential high dose chemotherapy in patients with advanced breast cancer.

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.

Burkitt's lymphoma in the appendicular skeleton.

Of 290 Ugandan children and adolescents with proven Burkitt's lymphoma 11 had lesions in the long bones or the pelvis. These started in the medulla as small osteolytic foci which coalesced and penetrated the cortex causing subperiosteal new bone formation in layers or spicules, and giving rise to large soft-tissue masses. Common sites were the femoral and tibial diaphyses and the metaphyses around the knee. Five were in the epiphyses. Other sites were the pelvis, humerus and ulna. One patient had a lymphomatous synovial effusion of the knee. In the lower limbs the lesions were often bilateral and symmetrical. Five patients had pathological fractures. Radiologically the lesions mimicked Ewing's sarcoma, osteosarcoma, osteomyelitis, acute leukaemia, syphilis and yaws, but clinically they were relatively painless, an important differential diagnostic feature. In the five patients with sustained remissions after chemotherapy the lesions and fractures healed well and the growth plates were undamaged.

Quality of life in developing countries.

PIP: 80% of cancers in developing countries present at an advanced stage and progress rapidly. Since ministries of health in these countries typically do not have the resources to afford aggressive responses to these conditions, the prevention and palliation of disease and related adverse circumstances are of paramount importance. To a clinical investigator, quality of life (QOL) is a measure of success in evaluating treatment outcomes; a means of assessing rehabilitation needs; and a predictor of response to treatment. It embraces broader functional domains than simply physical function and its measurement is likely to serve as a more accurate predictor of outcome than performance status alone. Under the aforementioned conditions under which cancer tends to present in developing countries, practitioners and programs should strive to attain the highest possible QOL for patients and families. Pain and distressing symptoms should be alleviated as much as possible. Socioeconomic and cultural aspects of developing countries are described followed by sections addressing QOL in terms of the impact of social influence; cultural influence on health, illness and QOL; measuring quality of life; and QOL studies in developing countries. Policy change is ultimately called for to ensure the constant availability of cheap analgesics, especially opioids, in a form easily transportable to rural areas. Essential drugs and priority on prevention and palliation are also needed; studies on QOL should help realize these goals.^ieng

Measuring quality of life in different cultures: translation of the Functional Living Index for Cancer (FLIC) into Chinese and Malay in Singapore.

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.