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V Torri

Publications and source records attributed to V Torri.

At least 19 recordsLinked to original sources
PubMed2002

First-line treatment for advanced ovarian cancer: paclitaxel, platinum and the evidence.

Four large randomised trials of paclitaxel in combination with platinum against a platinum-based control treatment have now been published in full, representing around 88% (3588 out of 4057) of patients randomised into the eight known trials of this question. There is substantial heterogeneity in the results of these four trials. Four main explanations for this heterogeneity have been proposed: differences in the extent and timing of 'crossover' to taxanes in the control groups; differences in the types of patient included; differences in the effectiveness of the research regimens used; differences in the effectiveness of the control regimens used. In this study we examine whether any of these explanations is consistent with the pattern of results seen in these trials. Each explanation suggests that a particular characteristic of each trial was responsible for the results observed. For each explanation the trials were split into groups according to that characteristic, in order to partition the total heterogeneity into that seen 'within' and 'between' groups of trials. If a particular explanation was consistent with the pattern of results, we would expect to see relatively little heterogeneity within each group of trial results viewed in this way, with most of the heterogeneity being between groups which are dissimilar with respect to the key characteristic. Heterogeneity 'within' and 'between' groups was formally compared using the F-ratio. If any explanation appeared to be consistent with the results of the trials, it was considered whether the explanation was also consistent with other evidence available about these regimens. Only one explanation appeared to be consistent with the pattern of results seen in these trials, and that was differences in effectiveness of the control arms used in these trials. This suggests that the very positive results in favour of paclitaxel/cisplatin seen in two of the trials may have been due to the use of a suboptimal control arm. There is no direct evidence about the relative effectiveness of the control arms used in these trials, but indirect evidence is consistent with the conclusion that the cyclophosphamide/cisplatin regimen used in two of the trials may be less effective than the control regimens used in the other trials. Specific concerns about the choice of a cyclophosphamide/cisplatin control arm in the first of these trials to report were raised before the results of the other trials were known, i.e. before any heterogeneity had been observed. Further investigation of this question would be useful. In the meantime, given all of the randomised evidence on the efficacy and toxicity associated with the regimens used in these trials, we conclude that single agent carboplatin is a safe and effective first-line treatment for women with advanced ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens.

PURPOSE: To assess the activity, efficacy, and tolerability of single-agent paclitaxel and a platinum-containing regimen in previously treated patients with recurrent ovarian cancer. PATIENTS AND METHODS: Patients who achieved complete remission with platinum-based regimens and whose disease recurred after a progression-free interval of more than 12 months were included in the study. Every 21 days, patients received paclitaxel 175 mg/m(2) intravenously (IV) over 3 hours or cyclophosphamide 500 mg/m(2), doxorubicin 50 mg/m(2), and cisplatin 50 mg/m(2) (CAP) IV. RESULTS: Between June 1992 and May 1995, 97 consecutive patients with assessable or measurable disease were randomized to paclitaxel (n = 50) or CAP (n = 47). The median number of cycles on each arm was six. Toxicities included grade 3/4 leukopenia (4% for paclitaxel v 34% for CAP), grade 3/4 neutropenia (13% v 36%), grade 1/2 myalgia (19% v 4%), allergic reactions (15% v 2%), and grade 2/3 nausea and vomiting (17% v 51%). Complete responses were achieved in 17% and 30% of patients receiving paclitaxel and CAP, respectively, and partial responses were achieved in 28% and 25%, respectively (P =.062). At a median follow-up time of 49 months, median progression-free intervals were 9 months for paclitaxel and 15.7 months for CAP (Cox analysis: hazards ratio [HR], 0.60; 95% confidence interval [CI], 0.37 to 0.97; P =.038); median overall survival times were 25.8 months for paclitaxel and 34.7 months for CAP (Cox analysis: HR, 0.58; 95% CI, 0.34 to 0.98; P =.043). CONCLUSION: Rechallenge with either single-agent paclitaxel or platinum-based chemotherapy is effective in this patient population. Preliminary results suggest that single-agent paclitaxel may not be as active as platinum-based chemotherapy in recurrent ovarian cancer. Larger randomized trials are needed.

Adult↗
PubMed2001

Early stage ovarian cancer: the Italian contribution to clinical research. An update.

Early ovarian cancer (stages IA-IIA) accounts for 30% of all epithelial ovarian cancer. Even if relatively uncommon, when "high risk" patients are considered, it is lethal in 25-30% of the cases. Mainstay of treatment is surgery followed by either adjuvant chemotherapy or radiotherapy when indicated on the basis of still debatable prognostic factors. Literature data show a great variability in survival rate due to the great heterogeneity of patients considered in different reports and few randomized trials affected by a consequent low power. Italian groups have contributed both in investigating the role of surgery and of chemo or radiotherapy in the treatment of this disease. An important contribution in surgery has been made by Italian institutions in reducing the extent of surgery in young patients wishing to retain their reproductive capability showing that a "conservative surgery" (unilateral oophorectomy) can be safely performed in initial stages without affecting the probability of cure. Another important surgical topic investigated by Italian institutions concerns the role of lymphadenectomy. In early ovarian cancer the node involvement ranges between 14-24% in stage I and 37-50% in stage II. Although the node positivity rate detectable by sampling (SA) is lower than the one shown by a systematic procedure (LY), no data at the moment show that patients undergoing a sampling evaluation have a poorer prognosis. From 1992 through 1994, 202 patients (SA: 99; LY: 103) were enrolled by six Italian institutions in a randomized trial aimed to assess the diagnostic and therapeutic role of SA vs. LY in early stage ovarian cancer. Positive nodes were detected in 9.9% vs. 19.3% respectively as well as a different proportion of intra/perioperative complications occurred. No difference in time to relapse nor in overall survival were detected in the two groups showing no evidence of efficacy in favor of extensive staging of the retroperitoneum. From 1983 to 1990, 271 stage I ovarian cancer patients entered two prospective multicentric randomized trials conducted by Italian institutions. Trial I compared cisplatin (50 mg/m2, six cycles repeated every 28 days) vs. no further treatment in stage IA-B grade 2-3 patients; Trial II compared the same dose and schedule of cisplatin vs. intraperitoneal P32 in stage IC patients. Cisplatin significantly reduced the relapse rate by 65% in Trial I and by 61% in Trial II, but survival was not affected (Trial I: HR = 1.15, 95% CI = 0.44-2.98; Trial II: HR = 0.72, 95% CI = 0.37-1.43). The final conclusion drawn by these two important Italian studies was that adjuvant cisplatin treatment in early ovarian cancer prevents relapse although the impact of chemotherapy remains unclear. For this reason two international trials have been performed (ICON1 and ACTION) aimed at assessing the role of platinum-based chemotherapy on survival. Italian collaboration in both trials has been important, including about half of the total number of the 900 randomized patients. Results will probably be available during this year and are expected with a great interest by the whole scientific international community.

Adult↗
PubMed2001

Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients.

OBJECTIVE: To evaluate the recently discovered long pentraxin PTX3 in plasma of critically ill patients and to compare it with the classic short pentraxin C-reactive protein and with other indicators of inflammation. DESIGN: A cohort study on plasma samples. SETTING: Medical intensive care unit (ICU) of the University Hospital of Basel. PATIENTS: A total of 101 consecutive critically ill patients admitted to the medical ICU. INTERVENTIONS: Venous blood samples were routinely obtained at entry, on day 2, and at discharge or before death. MEASUREMENTS AND MAIN RESULTS: Plasma samples were obtained from 101 consecutive critically ill patients admitted to the ICU with systemic inflammatory response syndrome, sepsis, or septic shock. PTX3 plasma levels were measured by enzyme-linked immunosorbent assay. PTX3 was elevated in critically ill patients, with a gradient from systemic inflammatory response syndrome to septic shock. PTX3 levels correlated with clinical scores reflecting severity of disease (e.g., Acute Physiology and Chronic Health Evaluation II: p =.00097). In addition, high levels of PTX3 were associated with unfavorable outcome. CONCLUSIONS: The long pentraxin PTX3 is elevated in critically ill patients and correlates with severity of disease and infection. Compared with the short pentraxin C-reactive protein, PTX3 may be a more direct indicator of tissue involvement by inflammatory and infectious processes.

Acute-Phase Proteins↗
PubMed2000

Antibiotics for preventing respiratory tract infections in adults receiving intensive care.

OBJECTIVES: Pneumonia is an important cause of mortality in intensive care units. The objective of this review was to assess the effects of antibiotics for preventing respiratory tract infections and overall mortality in adults receiving intensive care. SEARCH STRATEGY: We searched MEDLINE, proceedings of scientific meetings and reference lists of articles from January 1984 to September 1997. We also contacted investigators in the field. SELECTION CRITERIA: Randomised trials of antibiotic prophylaxis for respiratory tract infections and deaths among adult intensive care unit patients. DATA COLLECTION AND ANALYSIS: Trials were assessed for quality and investigators contacted for additional information. MAIN RESULTS: Overall 33 trials involving 5727 people were included. There was variation in the antibiotics used, patient characteristics and the risk of respiratory tract infections and mortality in the control groups. In 16 trials (involving 3493 patients) of a topical and systemic antibiotic combination, the average rates of respiratory tract infections and deaths in the control group were 33% and 28% respectively. There was a significant reduction of both respiratory tract infections (odds ratio 0.36, 95% confidence interval 0.30 to 0. 43) and total mortality (odds ratio 0.80, 95% confidence interval 0. 68 to 0.93). On average five patients needed to be treated to prevent one infection and 23 treated to prevent one death. In 17 trials (involving 2366 patients) of topical antimicrobials the rates of respiratory tract infections and deaths in the control groups were 30% and 24% respectively. There was a significant reduction of respiratory tract infections (odds ratio 0.57, 95% confidence interval 0.46 to 0.69) but not in total mortality (odds ratio 1.01, 95% confidence interval 0.84 to 1.22). REVIEWER'S CONCLUSIONS: A combination of topical and systemic prophylactic antibiotics can reduce respiratory tract infections and overall mortality in adult patients receiving intensive care. [This abstract has been prepared centrally.]

Adult↗
PubMed2000

Survey on the treatment of non-small-cell lung cancer in Italy.

BACKGROUND: The results of the Italian part of an international survey on therapeutic preferences and opinions about prognosis of patients affected by non-small-cell lung cancer (NSCLC) are shown. PATIENTS AND METHODS: The investigation was conducted by the means of a postal questionnaire aiming to gather information on preferences about treatment and beliefs about survival of three hypothetical patients affected by NSCLC in different stages (T2N1M0, T2N3M0, M1); three sources of Italian physicians potentially treating patients affected by NSCLC were the target population: participants in the Adjuvant Lung Project Italy (Alpi) trial, a 20% random sample of the Italian Medical Oncology Association (AIOM) and representatives of almost all the pneumology wards in Italy. RESULTS: Overall, there were 287 evaluable responses, 89% of respondents were males, mean age was 46 years, years from graduation 21 and charge of patients per clinician 82. The most important result is the wide variation of answers both about therapy and prognosis. Expectations about size of prognosis improvement with a new chemotherapy seem to be excessive. CONCLUSIONS: The results are discussed in relation to the twin surveys of Canada and England and Wales and to the meta-analyses on the efficacy of chemotherapy as an adjunct to primary treatment and on postoperative radiotherapy in non-small-cell lung cancer.

Adult↗
PubMed2000

Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: a meta-analysis of published randomised trials. A study of the GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente).

BACKGROUND: Several studies have investigated the possible role of the adjuvant chemotherapy after curative resection for gastric cancer failing to show a clear indication; previous meta-analyses suggested small survival benefit of adjuvant chemotherapy, but the statistical methods used were open to criticisms. MATERIALS AND METHODS: Randomised trials were identified by means of Medline and CancerLit and by selecting references from relevant articles. Systematic review of all randomised clinical trials of adjuvant chemotherapy for gastric cancer compared with surgery alone, published before January 2000, were considered. Pooling of data was performed using the fixed effect model. Death for any cause was the study endpoint. The hazard ratio and its 95% confidence intervals (95% CI), derived according to the method of Parmar, were the statistics chosen for summarising the relative benefit of chemotherapy versus control. RESULTS: Overall 20 articles (21 comparisons) were considered for analysis. Three studies used single agent chemotherapy, seven combination of 5-fluorouracil (5-FU) with anthracyclin, ten combination of 5-FU without anthracyclines. Information on 3658 patients, 2180 deaths, was collected. Chemotherapy reduced the risk of death by 18% (hazard ratio 0.82, 95% CI: 0.75-0.89, P < 0.001). Association of Anthracyclines to 5-FU did not show a statistically significant improvement when compared with the effect of the other regimens. CONCLUSIONS: Chemotherapy produces a small survival benefit in patients with curatively resected gastric cancer. However, taking into account the limitations of literature based meta-analyses, adjuvant chemotherapy is still to be considered as an investigational approach.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

The long-term prognostic significance of repeated blood pressure measurements in the elderly: SPAA (Studio sulla Pressione Arteriosa nell'Anziano) 10-year follow-up.

BACKGROUND: In young and middle-aged people, both systolic (SBP) and diastolic (DBP) blood pressure have a continuous, strong, and independent relationship with subsequent cardiovascular morbidity and mortality. These relationships are not well documented in older people and, until now, studies in the elderly do not provide homogeneous results on the importance of DBP compared with SBP as a cardiovascular risk factor. OBJECTIVE: To determine whether SBP and DBP are independent indicators of mortality risk in the elderly. DESIGN: An observational prospective cohort study to analyze the long-term prognostic significance of repeated SBP and DBP measurements in the elderly. PATIENTS AND METHODS: A total of 3858 outpatients 65 years or older (mean age [SD], 72.9 [4.9] years, 43.5% men) were selected randomly by 444 Italian National Health Service general practitioners in 1983. The population was followed up for 10 years. Crude and adjusted incidence rates of total and cardiovascular mortality were analyzed for classes of SBP and DBP based on the values recorded at the 2 initial visits 1 week apart and those measured during the first 12 months of follow-up. RESULTS: During the 10-year follow-up, 74 patients (1.9%) were lost to follow-up and 1561 (41.3%) died, 709 (45.4% of all deaths) from cardiovascular causes. A positive continuous, graded, strong, and independent association was observed with both total (P<.001) and cardiovascular (P<.001) mortality for SBP but not for DBP. The pattern was similar in both sexes, in persons younger and older than 75 years, regardless of preexisting cardiovascular diseases, and whether they had been receiving antihypertensive treatment at baseline. There was no J-shaped mortality curve in the subjects with the lowest SBP and DBP. CONCLUSIONS: These findings suggest that SBP, but not DBP, is a strong, positive, continuous, independent indicator of mortality risk in the elderly and should be stressed much more than DBP in the diagnosis and treatment of hypertension in this age group.

Aged↗
PubMed1999

Long-term follow-up of isolated optic neuritis: the risk of developing multiple sclerosis, its outcome, and the prognostic role of paraclinical tests.

We evaluated the risk of developing clinically definite multiple sclerosis (CDMS) after an acute attack of isolated optic neuritis (ON) in 112 patients, in relation to demographic and paraclinical findings. Patients were examined by brain MRI, CSF analysis, and multiple evoked potentials (EPs); 10 were lost to follow-up, and the other 102 were enrolled in a prospective study (follow-up duration 6. 3 +/- 2.2 years). Of these, 37 (36.3%) developed CDMS after a mean interval of 2.3 +/- 1.6 years. The risk of developing CDMS was 13% after 2 years, 30% after 4, 37% after 6, and 42% after 8 and 10 years. Gender, age, and season of ON onset did not affect the risk. MS occurred in 37 of 71 patients (52.1%) with one MRI lesion or more; no patient with a normal MRI developed the disease. MS developed more frequently in patients with intrathecal IgG synthesis than in those without (43% vs. 28%), but the difference was not statistically significant. Multiple EPs showed a slight predictive value only including somatosensory EPs of the lower limb. Multiple sclerosis was mild in most cases (EDSS 2.2 +/- 1.9). The EDSS was less than 4 in 32 cases (86%), between 4 and 6 in 2 (5%), higher than 6.5 in 3 (8%).

Adult↗
PubMed1998

Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.

Humans↗
PubMed1998

Elevated cerebrospinal fluid levels of monocyte chemotactic protein-1 correlate with HIV-1 encephalitis and local viral replication.

OBJECTIVE: To investigate whether the CC-chemokine monocyte chemotactic protein (MCP)-1 could play a role in the pathogenesis of HIV infection of the central nervous system. This hypothesis was suggested by previous observations, including our finding of elevated cerebrospinal fluid (CSF) levels of this chemokine in patients with cytomegalovirus (CMV) encephalitis. DESIGN AND METHODS: CSF levels of MCP-1 were determined in 37 HIV-infected patients with neurological symptoms, and were compared with both the presence and severity of HIV-1 encephalitis at post-mortem examination and CSF HIV RNA levels. MCP-1 production by monocyte-derived macrophages was tested after in vitro infection of these cells by HIV. RESULTS: CSF MCP-1 levels were significantly higher in patients with (median, 4.99 ng/ml) than in those without (median, 1.72 ng/ml) HIV encephalitis. Elevated CSF MCP-1 concentrations were also found in patients with CMV encephalitis and with concomitant HIV and CMV encephalitis (median, 3.14 and 4.23 ng/ml, respectively). HIV encephalitis was strongly associated with high CSF MCP-1 levels (P = 0.002), which were also correlated to high HIV-1 RNA levels in the CSF (P = 0.007), but not to plasma viraemia. In vitro, productive HIV-1 infection of monocyte-derived macrophages upregulated the secretion of MCP-1. CONCLUSIONS: Taken together, these in vivo and in vitro findings support a model whereby HIV encephalitis is sustained by virus replication in microglial cells, a process amplified by recruitment of mononuclear cells via HIV-induced MCP-1.

Adult↗
PubMed1998

GIVIO-SITAC 01: A randomized trial of adjuvant 5-fluorouracil and folinic acid administered to patients with colon carcinoma--long term results and evaluation of the indicators of health-related quality of life. Gruppo Italiano Valutazione Interventi in Oncologia. Studio Italiano Terapia Adiuvante Colon.

BACKGROUND: In 1989, the authors began a randomized trial to determine whether 5-fluorouracil and high dose folinic acid (HD-FUFA) would increase the event free and overall survival of patients with resectable Dukes B and C (AJCC/UICC Stage II and Stage III) colon carcinoma, and to assess the toxicity of the treatment and its impact on selected health-related quality-of-life indicators. Early results were published as a part of an international multicenter pooled analysis (IMPACT) in 1995. The purpose of this report is to update the survival data for patients enrolled in the trial and describe their reported perceptions of their own health and quality of life. METHODS: The trial involved multiple treatment centers, with a centralized randomization between surgery alone and surgery with chemotherapy. The HD-FUFA regimen employed consisted of 5-fluorouracil (370 mg/m2) plus folinic acid (200 mg/m2) administered daily for 5 days every 4 weeks for 6 cycles. Patients' perceptions of their own health status were obtained by means of 3 self-administered questionnaires, which were completed by patients at the time of discharge from the treatment center and at 6 and 24 months after randomization. RESULTS: Overall, 888 patients with resected Dukes B2 and C colon carcinoma were enrolled in the trial. HD-FUFA significantly reduced mortality by 25% (95% confidence interval, 5-41%; P=0.02) and events by 31% (95% confidence interval, 14-45%; P < or = 0.001). Compliance with treatment was good; more than 80% of patients completed the planned therapy. Toxicity was mild, and oral mucositis was the main side effect. None of the health-related quality-of-life parameters investigated (emotional status, worry about the future, changes in social life, impact of the disease, follow-up, and global quality of life) seemed to be affected by the treatment to which patients were allocated. A positive trend in the evolution of patients' psychologic status was observed. CONCLUSIONS: Long term results of this SITAC study confirm that HD-FUFA is a well-tolerated, effective 6-month adjuvant regimen for patients with colon carcinoma that has no detrimental effect on their quality of life.

Adult↗
PubMed1998

Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials.

OBJECTIVE: To determine whether antibiotic prophylaxis reduces respiratory tract infections and overall mortality in unselected critically ill adult patients. DESIGN: Meta-analysis of randomised controlled trials from 1984 and 1996 that compared different forms of antibiotic prophylaxis used to reduce respiratory tract infections and mortality with aggregate data and, in a subset of trials, data from individual patients. SUBJECTS: Unselected critically ill adult patients; 5727 patients for aggregate data meta-analysis, 4343 for confirmatory meta-analysis with data from individual patients. MAIN OUTCOME MEASURES: Respiratory tract infections and total mortality. RESULTS: Two categories of eligible trials were defined: topical plus systemic antibiotics versus no treatment and topical preparation with or without a systemic antibiotic versus a systemic agent or placebo. Estimates from aggregate data meta-analysis of 16 trials (3361 patients) that tested combined treatment indicated a strong significant reduction in infection (odds ratio 0.35; 95% confidence interval 0.29 to 0.41) and total mortality (0.80; 0.69 to 0.93). With this treatment five and 23 patients would need to be treated to prevent one infection and one death, respectively. Similar analysis of 17 trials (2366 patients) that tested only topical antibiotics indicated a clear reduction in infection (0.56; 0.46 to 0.68) without a significant effect on total mortality (1.01; 0.84 to 1.22). Analysis of data from individual patients yielded similar results. No significant differences in treatment effect by major subgroups of patients emerged from the analyses. CONCLUSIONS: This meta-analysis of 15 years of clinical research suggests that antibiotic prophylaxis with a combination of topical and systemic drugs can reduce respiratory tract infections and overall mortality in critically ill patients. This effect is significant and worth while, and it should be considered when practice guidelines are defined.

Administration, Topical↗
PubMed1998

Cyclophosphamide in chronic progressive multiple sclerosis: a comparative study.

No effective treatment is presently available for progressive multiple sclerosis (MS). Cyclophosphamide (CFX), a cytotoxic immunosuppressive drug widely used in systemic dysimmune diseases, has been proposed for the treatment of multiple sclerosis with different schedules and controversial results. To evaluate the safety and clinical efficacy of CFX, we compared three different treatment schedules in patients with progressive MS: induction followed by bimonthly boosters for one year (17 patients); bimonthly boosters for one year without previous induction (15 patients); and monthly boosters for one year (21 patients). Survival analysis showed that the percentage of stable patients was significantly higher in the first and third treatment schedule groups. Myelotoxicity occurred in patients treated with induction and boosters (Group A). A high incidence of broncopneumonia was observed in patients undergoing the second treatment schedule (Group B). No major effects were observed in patients treated with monthly boosters (Group C). Response to treatment was limited to secondary progressive form. This study suggests that monthly treatment with CFX might be safely administered in progressive MS patients; its clinical efficacy must be confirmed by an appropriately designed clinical trial.

Adult↗
PubMed1998

Hematotoxicity on human bone marrow- and umbilical cord blood-derived progenitor cells and in vitro therapeutic index of methoxymorpholinyldoxorubicin and its metabolites.

PURPOSE: MMDX [3'-deamino-3'-[2(S)-methoxy-4-morpholinyl] doxorubicin], an anthracycline derivative active in vitro and in vivo against multidrug-resistant tumors, is currently under investigation in phase I clinical trials. In vivo it is metabolically activated, resulting in more cytotoxic compounds. We determined in vitro the toxic concentration of a 1-h period of exposure to doxorubicin (DX), MMDX, and bioactivated MMDX on hematopoietic progenitors and tumor cell lines. METHODS: DX and MMDX were tested on both bone marrow- (BM) and cord blood (hCB)-derived clonogenic cells, whereas the metabolites were tested on hCB only. All substances were tested on seven tumor cell lines. RESULTS: BM cells proved to be twice as sensitive as hCB cells to cytotoxics, and MMDX was twice as toxic as DX against hCB cells; MMDX activated with normal rat-liver microsomes and with dexamethasone-induced rat microsomes were, respectively, 70 and 230 times more toxic than MMDX. A comparison of the cytotoxic concentrations on hematopoietic progenitors and tumor cells, revealed that DX and MMDX had 5-fold stronger activity on tumor cell lines than on granulocyte/macrophage colony-forming cells (GM-CFCs), whereas bioactivated MMDX showed comparable cytotoxicity against tumor cells and hematopoietic progenitors. CONCLUSIONS: MMDX metabolites are very potent but display a lower degree of tumor selectivity than MMDX. Strategies to reduce MMDX metabolization should be developed to optimize the therapeutic index of this new anthracycline.

Antibiotics, Antineoplastic↗