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Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested whether three-month FOLFOX or XELOX therapy produced changes in plasma amino acid levels (PAAL) (an estimation of whole-body amino acid metabolism) and in plasma levels of malondialdehyde (MDA), a marker of lipid hyper oxidation. Fourteen ambulatory, resected patients with colorectal cancer scheduled to receive FOLFOX (n = 9) or XELOX (n = 5) therapy, after overnight fasting, underwent peripheral venous blood sampling, to determine PAAL and MDA before, during, and at the end of three-month therapy. Fifteen healthy matched subjects (controls) only underwent measures of PAAL at baseline. The results showed changes in 87.5% of plasma essential amino acids (EAAs) and 38.4% of non-EAAs in patients treated with FOLFOX or XELOX. These changes in EAAs occurred in two opposite directions: EAAs decreased with FOLFOX and increased or did not decrease with XELOX (interactions: from p = 0.034 to p = 0.003). Baseline plasma MDA levels in both FOLFOX and XELOX patients were above the normal range of values, and increased, albeit not significantly, during therapy. In conclusion, three-month FOLFOX or XELOX therapy affected plasma EAAs differently but not the baseline MDA levels, which were already high.

Chemotherapy for colorectal cancer may lower muscle protein synthesis and increase oxidative stress. We hypothesize that chemotherapy may worsen plasma amino acids (AAs) and markers of oxidative stress (MOS). Therefore, this study aimed to document plasma AAs and MOS before, during and after chemotherapy in colorectal cancer (CRC) surgery patients. Fourteen normal-weight CRC patients were enrolled one month after surgery and scheduled for oxaliplatin-fluoropyrimidine combination (XELOX) therapy. Venous blood samples for AA and MOS (malondialdehyde, MDA; 8-hydroxy-2'-deoxyguanosine, 8-OHdG) measurements were drawn in fasting patients before each oxaliplatin infusion at initiation (A), 1 month (B) and 3 months (C) of the therapy, and after XELOX had finished (6 months, D). The results showed that during XELOX therapy (from phase B to phase D), in comparison to baseline (phase A), the branched chain amino acid/essential amino acid ratio, branched chain amino acids expressed as a percentage of total AAs, and arginine expressed as a percentage of total AAs significantly decreased ( p = 0.017, p = 0.028, p = 0.028, respectively). Plasma levels of MOS did not change significantly. This study indicates that XELOX therapy does not affect plasma AA levels or worsen oxidative stress.

Background: Pancreatic adenocarcinoma is a high-mortality neoplasm with a documented 5-years-overall survival around 5%. In the last decades, a real breakthrough in the treatment of the disease has not been achieved. Here we propose a prospective, phase II, multicentre, single-arm study aiming to assess the efficacy and the feasibility of a therapeutic protocol combining chemotherapy, carbon ion therapy and surgery for resectable and borderline resectable pancreatic adenocarcinoma., Method: The purpose of this trial (PIOPPO Protocol) is to assess the efficacy and the feasibility of 3 cycles of FOLFIRINOX neoadjuvant chemotherapy followed by a short-course of carbon ion radiotherapy (CIRT) for resectable or borderline resectable pancreatic adenocarcinoma patients. Primary outcome of this study is the assessment of local progression free survival (L-PFS). The calculation of sample size is based on the analysis of the primary endpoint "progression free survival" according to Fleming's Procedure., Discussion: Very preliminary results provide initial evidence of the feasibility of the combined chemotherapy and CIRT in the neoadjuvant setting for resectable or borderline resectable pancreatic cancer. Completion of the accrual and long term results are awaited to see if this combination of treatment is advisable and will provide the expected benefits., Trial Registration: ClinicalTrials.gov Identifier: NCT03822936 registered on January 2019.

Aims and Background: Palonosetron, a unique second-generation 5-HT3 receptor antagonist, has been demonstrated to control emesis related to chemotherapy-induced nausea and vomiting (CINV). The aim of this study was to evaluate the efficacy and tolerability of palonosetron followed by a single dose of dexamethasone in patients with breast cancer (BC) or colorectal cancer (CRC) receiving moderate emetogenic chemotherapy (MEC)., Methods and Study Design: Chemotherapy-naive BC and CRC patients were given MEC as adjuvant or first-line treatment. Palonosetron (0.25 mg IV) and dexamethasone (8 mg IV) were administered before chemotherapy on day 1. The primary endpoint was complete response (CR; no vomiting and no use of rescue medication) during the overall study period (days 1-5). The antiemetic response was evaluated during the acute (day 1) and delayed (days 2-5) phases., Results: Sixty-eight patients were enrolled (median age 61 years, 56 females; BC = 40, CRC = 28). CR was observed in 46 of 68 patients (67.6%), while CR during the acute and delayed phases was 75.0% in each cancer group. The antiemetic regimen was well tolerated., Conclusions: A single administration of palonosetron and dexamethasone on day 1 in BC and CRC patients adequately controls CINV during the entire period of emetic risk.

Background: Despite the consistent clinical results demonstrated by studies on anti-angiogenic drugs targeted against the vascular endothelial growth factor in metastatic colorectal cancer (mCRC) patients, no specific direct/indirect biomarker of their efficacy has been validated. In this field, circulating endothelial cells (CECs) and endothelial progenitor cells (CEPs) have recently been proposed as noninvasive biomarkers., Patients and Methods: The absolute numbers of CEPs, total CECs (tCECs) and their resting (rCECs) and activated subsets were evaluated by multiparameter flow cytometry in 40 mCRC patients at baseline and before the administration of the third and sixth course of a bevacizumab-based first-line treatment. Fifty healthy subjects were utilized as control., Results: The overall response rate was 80%, overall clinical benefit was 90% and median progression-free survival (PFS) was 13.8 months. In our patients, tCECs and rCECs were significantly increased compared with healthy subjects. The patients who achieved a radiological response showed, at baseline, a significant decrease of rCECs and a trend in decrease of tCECs in comparison with patients not achieving response. Finally, a baseline absolute number of tCEC and rCEC <40 cells/ml was evidenced in patients with a longer PFS. No correlation was found regarding CEP., Conclusions: Our study suggests significant correlations between both tCEC and rCEC baseline levels and the antitumor efficacy of a bevacizumab-based combination therapy in mCRC patients, thus confirming that these biomarkers could be used in the clinical setting as an early predictor of tumor response.

Background: In advanced colorectal cancer (ACC), FOLFOX4 has been accepted as a standard chemotherapeutic regimen. Due to the neurotoxicity induced by oxaliplatin, which occurs in about 50% of patients during the 6-month FOLFOX4 regimen, and the frequent need for hospitalization, alternative regimens may be required. We aimed to determine whether a 'maintenance' therapy with oral UFT (uracil-tegafur) in patients responding to FOLFOX4 is able to maintain the response and improve the quality of life (QoL) as a result of the outpatient regimen and lower psychological distress., Methods: Untreated patients with ACC who did not progress after 6 months of FOLFOX4 received oral UFT until disease progression or unacceptable toxicity. The aim of the study was to maintain the response obtained with the FOLFOX4 regimen for at least 6 months. The secondary objective was to evaluate QoL during the two different treatment regimens utilizing the 36-item Short Form Health Survey (SF-36)., Results: From January 2003 to August 2004, out of the enrolled 30 patients [22 males and 8 females; 2 patients with a complete response (CR), 14 patients with a partial response (PR) and 6 patients in stable disease (SD) after 6 months of FOLFOX4] 22 continued therapy with UFT until progression without significant toxicity; the remaining 8 patients (27%) had progressive disease (PD) during or at the end of FOLFOX4 and were treated with other regimen. After 6 months of UFT, 4 patients (13%) had CR, 6 patients (20%) PR and 4 patients (13%) SD; 16 patients (53%) progressed. Median follow-up was 31 months [interquartile range (IQR): 20-31 months]; 14 patients died of PD. The median time to progression was 13.9 (IQR: 7.7-20.1) months and the median survival time was 31 months (IQR: 20-31 months). Evaluation of QoL demonstrated a trend towards better QoL during UFT treatment., Conclusions: These results support the feasibility of maintaining good response and improving QoL (measured by SF-36) with an oral fluoropyrimidine after combination chemotherapy in ACC patients; moreover, since UFT can be used orally, patient compliance is increased and the duration of hospitalization can be decreased., ((c) 2008 S. Karger AG, Basel)

Aims and Background: Sequential docetaxel and gemcitabine following initial docetaxel plus epirubicin or vinorelbine association could be worthwhile as first-line treatment of metastatic breast cancer., Methods: Fifty-eight patients entered a phase II study that included two sequential phases. In the first phase, 36 and 22 patients previously unexposed or exposed to adjuvant anthracyclines received the association of docetaxel (75 mg/m2, day 1) with epirubicin (75 mg/m2, day 1) or vinorelbine (20 mg/m2, days 1 and 5), respectively, every 21 days for 4 courses. In the second phase, patients who had a response (R) or stable disease (SD) received docetaxel (35 mg/m2) and gemcitabine (800 mg/m2) on days 1, 8 and 15 every 28 days for 4 courses., Results: In the first phase, grade > or = III neutropenia occurred in 51% and 37% of patients during docetaxel-epirubicin and docetaxel-vinorelbine, respectively. In the second phase, it occurred in the 27% and 15% of patients initially treated with docetaxel-epirubicin and docetaxel-vinorelbine, respectively. On an intention to treat basis, the complete (CR) + partial response (PR) rate to the first phase was 71%, and 22% of patients had SD, without a significant difference between the docetaxel-epirubicin and docetaxel-vinorelbine arms. After the second phase, the CR + PR rate was 65%, and 14% of patients had SD. Median time to progression and survival were 12.1 and 22.0 months, respectively, without a significant difference between patients initially treated with docetaxel-epirubicin and docetaxel-vinorelbine., Conclusions: Following an initial docetaxel-based treatment, weekly docetaxel and gemcitabine maintains high percentages of R and SD, with improved toxicity. Survival was similar in patients previously untreated and treated with adjuvant anthracyclines.

In this study we evaluated whether a good response to conventional chemotherapy, i.e. a significant tumour reduction, is a prerequisite for improved survival in multiple myeloma (MM). Between January 1987 and March 1990, 341 consecutive previously untreated patients with MM received chemotherapy within the prospective, multicentre, randomised Protocol MM87. Of these, 258 patients were evaluable for both response and long-term survival and 244 (94.6%) have died. The median survival of all patients was 40 months (6-162 months). The median survival did not differ between patients who had complete response (CR) (50 months (9-162 months)), partial response (PR) (46 months (8-147 months)) or stable disease (SD) (41 months (7-135 months)). The median survival was shorter (13.6 months (6-135 months)) (P<0.0001) in patients whose disease progressed while they were receiving first induction chemotherapy. Causes of death were more frequently (P=0.04) related to MM in patients who had progressive disease (PD) than in patients who had a CR or PR or SD. The main clinical and laboratory characteristics were similar in the four groups. These data indicate that patients who maintain SD during first-line chemotherapy have a prognosis similar to that of patients who attain a response. Only patients whose disease progresses have a distinctly worse outcome.

Objective: This study was designed to determine the maximum tolerable dose (MTD) of gemcitabine plus docetaxel, both given on a weekly schedule, in patients with pretreated metastatic breast cancer (MBC)., Methods: Heavily pretreated patients with MBC, aged 18-75 years with World Health Organization performance status of 0-2 were enrolled. Three escalating weekly doses of docetaxel (30, 35 and 40 mg/m(2)) followed by a weekly fixed dose of gemcitabine, 800 mg/m(2), were administered on days 1, 8 and 15 of a 28-day cycle. Dose-limiting toxicity (DLT) included grade > 3 hematologic toxicity and grade > 2 stomatitis, asthenia, diarrhea or organ-specific toxicity (except alopecia). Dose escalation was stopped if > or = 3 of 5 patients at any dose level experienced DLT., Results: Eighteen patients (median age 56 years) received a mean of 4.1 (range 1-6) cycles. Asthenia, stomatitis and leukopenia were the main DLTs. One of 5 patients had DLT at dose level 1 and 2 of 5 patients at dose level 2. At dose level 3, 3 of 5 patients had DLTs. Three additional patients treated at dose level 3 confirmed that the MTD had been reached. Therefore, the recommended docetaxel dose in combination with gemcitabine 800 mg/m(2) for phase II studies was established at the next lower dose, 35 mg/m(2). Of 12 evaluable patients, 7 (58%) achieved an objective response., Conclusions: Gemcitabine 800 mg/m(2) plus docetaxel 35 mg/m(2) on days 1, 8 and 15 of a 28-day cycle is a safe regimen which shows activity in heavily pretreated patients with MBC. Further phase II investigations with this combination are now warranted., (Copyright 2002 S. Karger AG, Basel)

Sequential administration of the association of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel could be better tolerated than the association of an anthracycline and paclitaxel while having a similar antitumour effect. 69 patients with advanced breast cancer previously untreated with anthracyclines or paclitaxel entered a phase II multicentre study in which FEC was followed by paclitaxel. Both regimens were administered 4 times every 21 days. The median follow-up is 20 months and 38/69 patients have died. Grade III-IV toxicity was acceptable. Leukopenia occurred in 26% of patients, thrombocytopenia in 2% and anaemia in 4%. One patient had reversible heart failure during FEC therapy. Peripheral neuropathy and arthralgia-myalgia occurred in 9% and 4% of patients, respectively and one patient had respiratory hypersensitivity during paclitaxel treatment. 9 patients did not complete therapy because of: treatment refusal (n = 1), cardiac toxicity (n = 1), early death during FEC chemotherapy (n = 1), major protocol violations (n = 4), hypersensitivity reaction (n = 1) and early death during paclitaxel chemotherapy (n = 1). The overall response rate was 65% (95% CI = 53-76), and 7% of patients had stable disease. Therapy was defined as having failed in 28% of patients because they were not evaluable (13%) or had progressive disease (15%). The median time to progression and survival are 13.2 and 23.5 months, respectively. Sequential FEC-paclitaxel is a suitable strategy for patients with metastatic breast cancer who have not been previously treated with anthracyclines and/or taxanes. In fact, it avoids major haematologic toxicity and has a good antitumour effect., (Copyright 2001 Cancer Research Campaign http://www.bjcancer.com.)

With respect to their association, sequential non-cross-resistant cytostatics could be better tolerated and allow a similar antitumor effect. From January, 1998 to July, 1999, 42 consecutive patients with metastatic breast cancer (MBC) previously treated with anthracyclines as adjuvant- or first-line therapy entered a phase II multicenter study where docetaxel (TXT, 100 mg/m2/3 weeks/4 times) was followed by vinorelbine (VNR, 25 mg/m2/10 days/8 times). Median follow-up is 21 months and 22/42 patients have died. Four patients did not complete therapy due to early death, grade 3-4 gastrointestinal mucosytis (2 patients) and grade 3 neurotoxicity during TXT therapy. Overall response rate was 57%, and 5% of patients had stable disease. There were 38% of therapy failures due to non-evaluability (10%) or progressive disease (28%). Median time to progression and survival are 10.1 and 17.1 months. Sequential TXT-VNB is a suitable strategy for MBC patients previously treated with anthracyclines. It avoids haematologic toxicity and allows a good antitumor effect. Careful monitoring of intestinal mucosytis is required.

In metastatic breast cancer (MBC) doubling the epirubicin (EPI) dose intensity (DI) within the FEC (5-fluorouracil, EPI, cyclophosphamide) regimen could increase the response rate (RR) and ameliorate the quality of life (QoL) over standard FEC. From May, 1995, 74 consecutive patients with MBC were randomly treated with 6 courses of two FEC regimens containing 60 (60FEC) or 120 (120FEC, supported by primary G-CSF) mg/m2 of EPI. Drugs were administered every 21 days. The QoL was assessed over and after treatment by the EORTC QLQ-C30 (VER 2.0) and QLQ-BR23 questionnaires, compiled by the patient, and the Spitzer's QL-index, compiled by the physician. The study was prematurely closed in May, 1997, due to RR and QoL data of 4th interim analysis. The delivered EPI DI was 20.0 and 37.9 mg/m2/week in 60- and in 120FEC, respectively. Among the two regimens, there was no statistically significant difference in RR or in improvement of baseline overall QoL. With respect to 60FEC patients, the 120FEC patients had longer time to progression (19.2 vs 13.1 mos, p=0.04). Over baseline, the 120- but not the 60FEC patients had significantly greater pain decrease and lower deterioration of body image. In MBC, both 60- and 120FEC regimens furnished the same RR and improvement in overall baseline QoL. With respect to 60FEC patients, the 120FEC patients experienced longer time to progression. Over baseline, pain decrease and preservation of body image were also greater in these patients.

We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57-2.42; P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months; P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients.

Aims and Background: The neutropenia induced by six courses of an intensified FEC regimen is expected to be checked by early primary administration of G-CSF which is stopped eight days before the next chemotherapy course. Less information is available about megakaryocytic and erythroid toxicity over six courses., Methods and Study Design: Sixty-six consecutive patients with metastatic breast cancer completed six courses of a randomized treatment with two FEC regimens administered every 21 days, in which 600 mg/m2 of cyclophosphamide and 5-FUwas associated with 60 or 120 mg/m2 of epirubicin (60FEC, 35 patients, vs 120FEC, 31 patients). 120FEC was supported by early primary G-CSF (days 4 to 13). Blood counts were obtained seven times during each course., Results: The non-hematologic toxicity over 364 courses was similar in 60FEC and 120FEC. No cumulative hematologic toxicity was observed for white blood cells (WBC) and platelets (PLT), while for hemoglobin (Hb) a somewhat higher cumulative toxicity was observed with 120FEC than with 60FEC. WBC, PLT and Hb grade III-IV toxicity occurred in 40.1% and 45.6% (P=ns), in 23.1% and 0.8% (P <.0001) and in 15.6% and 3.0% (P <.005) of the two regimens, respectively. There were no febrile or hemorrhagic episodes. The epirubicin relative dose intensity delivered was 1.95 in 120FEC with respect to 60FEC., Conclusions: Our G-CSF schedule permitted to deliver six courses of 120FEC without any clinically relevant side effects. Grade III-IV leukopenia was similar with 120FEC and 60FEC, while grade III-IV thrombocytopenia and anemia occurred more often with 120FEC than with 60FEC.

Between May 1995 and July 1997, paclitaxel (TX) (175 mg/m2 by 3 h i. v. infusion every 21 days) was administered to 70 consecutive patients (median age: 57 years) previously treated with the FEC regimen (cyclophosphamide and 5-fluorouracil, 600 mg/m2, plus epirubicin, 60 or 120 mg/m2) as an adjuvant setting or as a first-line therapy for metastatic disease. Sixty-eight patients were evaluable for response, while two died early. Patients received a median of 4.7 (3-12 course) of TX for a total of 211 courses. The overall response and stable disease rate was 54% in 11 patients, who relapsed following adjuvant FEC, and 60% in 57 patients, who received FEC as first treatment for their metastatic disease. No complete respose was obtained. In patients pretreated for metastatic disease, response and stable disease rates were similar irrespective of previous response to FEC. Main hematologic toxicity of TX was of short duration, grade II/III leukopenia (86% of patients) and non-hematologic toxicity was grade II/III peripheral neuropathy, related to the cumulative dose of TX. At this schedule, TX offers a significant rate of partial responses or disease stabilization in patients with metastatic breast cancer previously treated with FEC.

In a multicentre study, 83 patients with advanced and previously uniformly treated multiple myeloma (MM) were randomised between cyclophosphamide (600 mg m-2) and epirubicin (70 mg m-2), administered every 3 weeks for three courses and both associated with prednisone and interferon-alpha2b. Both regimens were administered on an outpatient basis and had low haematological toxicity. Clinical results were similar. Overall response rate (43%) and median response and survival (5.9 and 14.1 months respectively) compare well with those obtained with more aggressive chemotherapy schedules.

Seventeen consecutive patients with previously untreated poor prognosis Hodgkin's disease (clinical stage II and III with systemic symptoms, and stage IV) received 6 courses of aggressive chemotherapy, with (9 patients) and without (8 patients) the addition of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF). Chemotherapy (MOPP/ABV/CAD regimen) included full doses of nitrogen mustard, lomustine (CCNU), vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine and bleomycin, and was administered between days 1 and 15 of each course. Course were planned for 28-day intervals. rhGM-CSF was given at a dose of 5 micrograms/kg/day subcutaneously from day 16 to 26 of each course. With cytopenia (i.e. white blood cell, WBC, count < 3.0 x 10(9)/L and/or platelet count < 100 x 10(9)/L) delaying courses was preferred to administering reduced drug dosages. Substantial delays (ranging from 7 to 28 days) in delivering cytostatics were necessary between 70% of courses. The cumulative mean number of days for which the courses had to be delayed before completing the 6 MOPP/ABV/CAD courses was 57. The percentage of planned doses of cytotoxic drugs (nitrogen mustard, melphalan, epidoxorubicin, procarbazine) actually administered was 92%. Causes of treatment delay were presented by leucopenia in 82% and by leuco-thrombocytopenia in 23% of the courses. The WBC nadir was constantly encountered at day 20-21 following completion of courses, and slightly worsened with subsequent courses. The decrease in platelet values was milder than that in WBC counts. There were no differences in any of the above parameters between patients treated with MOPP/ABV/CAD alone or followed by rhGM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

From October 1983 to December 1988, 84 consecutive adult patients with acute non-lymphoblastic leukaemia (ANLL; median age = 51 yr) were uniformly treated to induce remission (CR) with intravenous vincristine and cytarabine sequentially followed by daunomycin and infusion cytarabine. From October 1983 to December 1985 consolidation was non-intensive (2 courses with the same drugs used for induction) (protocol ANLL83: 27 patients, median age = 45). From January 1986 to December 1988 consolidation was intensive (4 courses of vincristine and cytarabine sequentially followed by etoposide plus thioguanine or amsacrine) (protocol ANLL86: 57 patients, median age = 57). Excluding early deaths, the CR rate was 71.6%. Median CR, responsive patient survival and overall survival were 11.1, 15.3 and 8.5 mo, respectively. For protocol ANLL83 and ANLL86, median CR was 8.7 and 13.2 mo (P less than 0.05) and median survival was 13.1 and 16.9 mo (P less than 0.05) for responders and 8.0 and 9.2 mo (P not significant) for all patients. Intensive consolidation including drugs not previously used for induction seems to prolong CR duration and responder survival in adult ANLL.

From 1986 to 1988, 54 consecutive previously untreated patients with acute non-lymphoblastic leukaemia (ANLL), median age 54 years, were treated for remission (CR) induction with vincristine and intravenous medium-dose cytarabine sequentially followed by daunomycin and infusion cytarabine. CR patients received intensive consolidation. Bone marrow blast kinetics was studied before therapy with in vivo bromodeoxyuridine and bivariate flow cytometry. CR rate was 70.2%, median CR was 13.2 months, responsive patient survival was 16.9 months and overall survival was 9.2 months. Besides lower median age, the 33 responsive patients also had shorter potential doubling time (Tpot) and greater cell production rate (PR) than the 14 unresponsive patients (mean values = 10.9 vs. 25.4 days, P less than 0.05, and 14.7 vs. 8.9 cells/100 cells/day, P less than 0.02, respectively), due to a higher mean labelling index (7.0 vs. 5.1%, P less than 0.05) and/or to a shorter mean DNA synthesis time (13.6 vs. 18.6 hours, P less than 0.05). Besides lower white blood cell count and bone marrow blast percentage, patients who experienced CR longer than 13.2 months had shorter Tpot (P less than 0.05) and a greater PR (P less than 0.02) than those who relapsed before this time. These data indicate that kinetic parameters have prognostic relevance in ANLL patients treated with sequential vincristine, cytarabine and daunomycin for inducing CR and with intensive consolidation after CR, a high proliferative activity being a favourable factor for both CR achievement and its duration.