In a prospective multicenter study, we analyzed the benefits of allogeneic bone marrow transplantation (BMT) in a nonselected group of adult patients with acute lymphoblastic leukemia (ALL) and, by a randomized trial, evaluated the effectiveness of autologous BMT over chemotherapy as postremission therapy in patients younger than 50 years who were not candidates for allogeneic BMT.

Immunosuppressive chemotherapy and bone marrow transplantation are increasingly used to treat and, in some cases, cure numerous malignant conditions. The systemic sequelae as a result of these immunosuppressive techniques lead to a host of oral and dental complications. The direct and indirect stomatotoxic effects lead to development of ulcerative, hemorrhagic, or infectious complications that potentially can lead to increased mortality and morbidity. Chlorhexidine was studied to evaluate its broad spectrum antimicrobial properties and to evaluate its effect on immunosuppression-induced mucositis. Our double-blind randomized study revealed that chlorhexidine versus controls had considerable effect in the bone marrow transplant cohort. Patients who received chlorhexidine while undergoing bone marrow transplantation were found to exhibit fewer and less painful mucositis lesions. This study supports prophylactic use of chlorhexidine in patients who undergo bone marrow transplantation.

The effect of a combination regimen using norfloxacin (NFLX) and amphotericin B (AMPH-B) for prevention of infections in patients with acute leukemia being treated by remission-induction chemotherapy in a randomized, controlled trial was studied. One hundred and six consecutive, evaluable patients were randomly assigned to receive orally 200 mg of norfloxacin two or four times daily and 200 mg of amphotericin B four times daily, or amphotericin B only. A smaller percentage of patients with bacteriologically-documented infections was observed in the study group compared with the control group (34.6% vs 56.9%; P < 0.05). The mean number of days that the patients received empirical antibiotic therapy was shorter in the study group (23 days vs 30 days; P < 0.05). The percentage of patients with a gram-negative bacterial infection (9.6% vs 27.5%; P < 0.05) or a fungal infection (17.3% vs 37.3%; P < 0.05) was decreased in the study group. This new combination antimicrobial regimen is safe and effective for prevention of gram-negative bacterial as well as fungal infections in patients with acute leukemia being treated with cytotoxic remission-induction chemotherapy.

Vitamin A and retinoids are strong inhibitors of epithelial cancer promotion and progression in experimental carcinogenesis. This study examined whether they may prevent the occurrence of upper aerodigestive cancer in subjects heavily exposed to tobacco smoking, such as patients already cured of an early-stage lung cancer.

Twenty-one patients with superficial bladder cancer entered an analysis of single dose (2'R)-4'-O-tetrahydropyranyladriamycin (THP) or adriamycin (ADM) administration. The patients in each group that have been or not have been treated previously with anti-cancer drugs were randomized into two groups, one was given THP and the other ADM. Thirty-mg of THP or ADM dissolved in 30 ml of physiologic saline was instilled into the bladder, and retained for 1 hour. After 1 hour retention of the drugs, tumor tissues and normal mucosas were removed by punch biopsy forceps transurethrally. The tissue concentrations of THP and ADM were estimated by high performance liquid chromatography. The tissue concentrations of THP and ADM in the tumors were significantly greater (p < 0.05) than those in the normal bladder mucosas. The tissue concentration of THP in the tumors were greater than that of ADM. The tissue concentrations of THP and ADM in the tumor of patients who have been treated with anti-cancer drugs previously were less than those of patients who have not. This results demonstrated that prior therapy with anti-cancer drug may cause a resistance for intravesical instillation chemotherapy. However in patients with prior therapy, the tissue concentration of THP in the tumors were greater than that of ADM. Based on these findings, THP has been shown to be were effective as an intravesical instillating agent especially, in cases with prior chemotherapy.

Although the effectiveness of antibiotic monotherapy in febrile neutropenic patients remains unproven, ceftazidime has been shown previously to be effective monotherapy for the empiric treatment of selective patients. The efficacy and safety of ceftazidime versus ceftazidime plus tobramycin was evaluated in the treatment of febrile children (range 8 months to 18 years) with neutropenia secondary to cancer chemotherapeutic agents. Of the evaluable 89 patients, 45 received ceftazidime and 44 received ceftazidime plus tobramycin for 5 to 10 days. At the end of therapy, 30 (67%) of the 45 ceftazidime-treated patients were clinically cured compared with 38 (86%) of 44 combination-treated patients. Thirteen (29%) of the patients treated with ceftazidime failed to respond clinically to treatment, versus four (9%) of the patients treated with ceftazidime/tobramycin (p = 0.046). This study suggests that ceftazidime as monotherapy in febrile neutropenic children may be inferior to combination therapy for optimal clinical response in these patients.

The perceived informativeness of a publication can be assessed by measuring the change in belief it induces among the scientific public, regarding a certain hypothesis. In a randomized trial, we studied the effect of empirical evidence from a clinical experiment and a case-control study on the hypothesis that beta-carotene protects against (cervical) cancer. The study population consisted of first authors of recently published patient-oriented research papers. They received an abstract of the clinical experiment, of the case-control study, or a "placebo" abstract. The latter was used to assess the specific effect of the empirical evidence in the two real studies. The change in belief in the hypotheses was expressed as a likelihood ratio (LR). All three abstracts led to a decrease in belief in the hypothesis. The median LRs of the abstracts of the experiment, case-control study and "placebo" were 0.33, 0.45, 0.75 respectively. This paper shows that the belief in a certain hypothesis is influenced by the quality of empirical evidence in a study. The magnitude of change induced by the experimental and case-control abstract had the anticipated order, but the change in belief induced by the "placebo" abstract was larger than we had expected. Reasons for this may be the concise information in the abstract and the variable methodological training of the study population.

After informed consent, 86 patients with advanced cancer undergoing potentially myelosuppressive cytotoxic chemotherapy were randomized to receive placebo or subcutaneous granulocyte-colony stimulating factor (G-CSF) 5 micrograms/Kg/day in order to prevent severe neutropenia and its related morbidity. The incidence of neutropenia (absolute neutrophil count < 1,000/mm3) was significantly reduced in patients receiving G-CSF than in controls (18% versus 42%; P < 0.05). The duration of neutropenia was also shortened by the administration of G-CSF (4.8 versus 8.2 days; P < 0.05). Therapy with G-CSF has also a positive impact on the dose-intensity of employed regimens. Patients treated with G-CSF showed oral fungal disease in 9% of cases, while control patients had a 21% incidence (NS). Patients treated with G-CSF received 91% of the programmed dose-intensity as compared to 71% of control patients (P < 0.05). These data strengthen the clinical usefulness of G-CSF in the prevention of chemotherapy-related neutropenia, infections, and reduction in dose-intensity. Further studies are required to establish if the increase in dose-intensity allowed by G-CSF treatment may positively influence the outcome of cancer patients.

A phase II study was conducted to evaluate the antitumor effect and toxicity of CPT-11 in patients with metastatic colorectal cancer.

In an effort to identify new active chemotherapeutic agents against non-small cell lung cancer (NSCLC), the authors conducted a randomized Phase II trial to evaluate the efficacy of amonafide or trimetrexate in patients with Stage IV disease.

The importance of dose intensity has not been clearly defined in ovarian cancer and we present a prospectively randomised trial of dose intensity in patients with ovarian cancer.

The observed activity of cisplatin in breast cancer and its unattractive toxicity profile in palliative treatment warranted further study of platinum analogues in this disease.

Patients with metastatic (stage IV) non-small-cell lung cancer usually have a poor prognosis and disease refractory to chemotherapy. Three new agents--taxol, merbarone, and piroxantrone--have shown promising antitumor treatment in vitro and in animals. Taxol is an antimicrotubular agent that interferes with mitosis during cell division. Merbarone, a conjugate of thiobarbituric acid and aniline, is a topoisomerase II inhibitor, which thus inhibits DNA synthesis and tumor growth. Piroxantrone, an anthracenedione derivative, is a DNA intercalating agent that has shown potent antitumor activity in animal studies.

Sixty cancer chemotherapy patients were randomly assigned to one of six conditions formed by a 3(cognitive distraction, relaxation training, no intervention) x 2(high anxiety, low anxiety) factorial design. All patients were followed for five consecutive chemotherapy sessions. Outcome measures included patient reports, nurse observations, and physiological indices. Results indicated that distraction patients reported less nausea prior to chemotherapy and lower systolic blood pressures after chemotherapy than controls. Relaxation training patients reported less nausea prior to chemotherapy and exhibited lower systolic and diastolic blood pressures after chemotherapy than control patients. There were no significant differences between distraction and relaxation training patients on any measure. Patients with high initial levels of anxiety exhibited continually elevated levels of distress throughout the chemotherapy experience; however, anxiety level did not interact with the effectiveness of the treatment interventions. Overall, the data support the use of both cognitive distraction and relaxation training for reducing the distress of chemotherapy with both high and low-anxiety patients and suggest that at least some of the effects of relaxation training can be achieved with distraction alone.

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was given to 60 patients, in a double-blind, non-prophylactic study of already established chemotherapy-induced leucopenia, for 5 days by continuous intravenous infusion and twice or once daily by subcutaneous injection. Four patients were randomized to rhGM-CSF (3) or placebo (1) at each dose (1.3, 1.7, 5.5, 11, or 22 micrograms of protein/kg). Leucocyte recovery was significantly enhanced compared with controls, in a dose-dependent manner except for 22 micrograms/kg which was ineffective with a worse experience of side effects in some patients. Most adverse events occurred in equal proportions in the treated and placebo cases. Fourteen patients developed infection and were treated with antibiotics in addition to rhGM-CSF. They were joined by a further 18 febrile patients and treated with rhGM-CSF in a subsequent open-label trial. The survival from infection was related to white blood cell (WBC) count: 19 of 32 responded with increased numbers of leucocytes (WBC count above 1.5 x 10(9)/1) after 5 days of GM-CSF. Sixteen of the 19 leucocyte 'responders' recovered from infection, two died from the underlying disease and one from persistent infection. Six of the 13 patients who did not have a leucocyte response died with persistent infection. These data indicate that rhGM-CSF enhances the leucocyte count following chemotherapy and in this way saves critically ill neutropenic patients from fatal infections.

To investigate the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on cytotoxic chemotherapy-induced granulocytopenia, we performed an open nonrandomized clinical trial in 46 patients with malignancies receiving cytotoxic chemotherapy regimen. Twenty-six patients who received two cycles of the identical chemotherapy regimen and had granulocytopenia less than 1 x 10(9) cells/l after the first cycle of chemotherapy were eligible for this study. They received 60, 125 or 250 micrograms/m2/day of rhGM-CSF randomly. The nadirs of peripheral granulocytes demonstrated significantly much higher levels in all dosages studied than those of control cycles. The duration of granulocytopenia was shortened with rhGM-CSF support. Such granulocyte recovery appeared in parallel with increasing dosages of GM-CSF, thus, infections with febrile episodes were reduced. Toxicity of rhGM-CSF was generally well tolerated.

Cicaprost is a new synthetic prostacylin analogue which is metabolically stable and bioavailable after oral administration; in previous studies it has been shown to have vasodilator antiplatelet effects. In this pilot study, we investigated the clinical efficacy of and patient tolerance to two dosage levels of cicaprost (2.5 micrograms tds and 5 micrograms tds) in the treatment of Raynaud's phenomenon secondary to systemic sclerosis (SSc). This was a three centre, double-blind, placebo controlled study of 49 patients carried out over four winter months. For a period of 10 days, 16 patients were given a placebo, 16 received cicaprost 2.5 micrograms tds and 17 received cicaprost 5 micrograms tds. Response was assessed based on the total number and duration of Raynaud's attacks, the average severity of the attacks, the number of painful attacks as a proportion of all attacks, a digital ulcer count, and the patients' opinion of the treatment. Although the clinical and laboratory parameters of digital vasospasm did not show statistically significant improvement in those who received cicaprost compared with those on the placebo, the severity of attacks lessened in the patients who received cicaprost 5 micrograms tds, and a statistically significant difference was seen in the average severity at week 2 post-treatment (p = 0.02). The apparent lack of overall significance was probably related to the short treatment period and relatively low doses of cicaprost used in this exploratory study. Longer studies with dose titration are probably needed to demonstrate the beneficial effects, if any, of cicaprost in patients with Raynaud's secondary to SSc, and these are being planned.

The cost effectiveness of ondansetron was compared with that of metoclopramide in the prevention of acute emesis due to highly emetogenic chemotherapy in an open, randomised, parallel group pilot study. Ondansetron was given as three 8 mg intravenous doses (0, 4 and 8 h) and metoclopramide as an intravenous loading dose (3 mg/kg) followed by a maintenance dose of 0.5 mg/kg/h for 8 h. Therapeutic outcomes and full utilisation costs, that is nursing time, material costs, in addition to drug acquisition prices were recorded for each antiemetic for 24 h following chemotherapy. The cost per successfully treated patient (< or = 1 emetic episode and no adverse events) was 95.20 pounds for ondansetron and 92.18 pounds for metoclopramide. The results of the study therefore suggest that for the control of acute emesis due to highly emetogenic chemotherapy ondansetron and metoclopramide are equally cost-effective treatments.

166 patients receiving moderately emetogenic chemotherapy were entered into a randomised prospective study in which the efficacy of single dose ondansetron 8 mg, tropisetron 5 mg and granisetron 3 mg in the prophylaxis of acute vomiting was evaluated. 130 patients were evaluable for analysis. During the 24 h following the start of chemotherapy complete control of vomiting was achieved in 80% [95% confidence interval (CI) 73.1; 86.9] of patients receiving granisetron compared with 75% (95% CI 67.1; 82.1) of those on tropisetron and 69% (95% CI 60.5; 76.5) on ondansetron. The patients experienced significantly fewer failures with granisetron (6.2%, 95% CI 2.1; 10.3) than with either ondansetron (14.6%, 95% CI 8.5; 20.6) or tropisetron (13.8%, 95% CI 7.9; 19.7). When asked, 34 (26%) patients out of 130 expressed no preference, 54 (42%) preferred granisetron, 22 (17%) preferred ondansetron and 20 (15%) preferred tropisetron. All the 5-HT3 receptor antagonists were highly effective in the prophylaxis of acute vomiting induced by moderately emetogenic chemotherapy. The observed differences in the control of emesis, although statistically significant, may not have clinical significance.