Biomedical subjects

S Jelić

Publications and source records attributed to S Jelić.

At least 19 recordsLinked to original sources

PubMed2002

Use of high-dose cytarabine to enhance cisplatin cytotoxicity-effects on the response and overall survival rates of advanced head and neck cancer patients.

UNLABELLED: It has been reported that cytarabine, acting by at least two different mechanisms, enhances the cytotoxic effect of cisplatin in in vitro systems. The aim of this open, prospective, randomised study was to estimate the eventual benefits from the inclusion of high-dose cytarabine in the cisplatin-5-fluorouracil (5-FU) regimen as first-line treatment of patients with advanced head and neck cancer. The study recruited successive patients with unresectable grade I/II head and neck cancer who were not suitable for irradiation treatment (T any N3 or T4 N2C), metastatic or previously irradiated. All patients gave their informed consent. A joint ear, nose and throat (ENT) oncological committee performed the selection. A total of 170 patients were included in the study. Patients randomised to arm A were given 1000 mg/m(2) cytarabine on day 1 preceding for 6 h cisplatin infusion, 30 mg/m(2)/24 h cisplatin intravenous (i.v.) bolus days 1-4 and 1000 mg/m(2)/24 h 5-FU in a 4-h infusion on days 1-4. Patients in arm B were given cisplatin and 5-FU in the same dosage and schedule as in arm A. Additional irradiation+/-surgery was performed if and when feasible. Patients in both arms were well balanced with regard to clinical variables. The following results were obtained: Arm A: 84 patients were included, 74 were evaluable for activity; RESPONSE: complete response (CR) 8 (11%), partial response (PR) 40 (54%), stable disease (SD) 11 (15%), progressive disease (PD) 15 (20%). The overall response rate (RR) based on the evaluable patients was 48/74 (65%, 95% confidence interval (CI) 54-75%); The RR based on an intent-to-treat analysis was 57%, 95% CI 47-67%; Median survival was 13 months; There were 50 episodes of granulocytopenia grade IV and 15 of febrile neutropenia per 316 cycles. Arm B: 86 patients were included, 80 were evaluable for activity; RESPONSE: CR 7 (9%), PR 29 (36%), SD 10 (12.5%), PD 34 (42.5%); The overall RR based on the evaluable patients was 36/80 (45%, 95% CI 35-56%); The RR based on an intent-to-treat analysis was 42%, 95% CI 32-52%; Median survival was 8 months; There were 14 episodes of granulocytopenia grade IV and 7 febrile neutropenias per 324 cycles. The RR was significantly higher in arm A (P=0.013), power (one-sided) 80%. The proportion of patients from the appropriate subset who achieved a clinical response making additional treatment feasible was higher in arm A (P=0.00015), as well as the proportion of patients with a performance status 2+3 achieving a response (P<0.0001). Using the Log-rank test, patients from arm A achieved a significantly longer survival (P=0.009), with the probability of survival at 12 months of 0.58 for patients in arm A and 0.28 for patients in arm B. Grade IV granulocytopenia and thrombocytopenia were more frequent in arm A. Due to its haematological side-effects, cytarabine might not be the ideal drug to modulate the cytotoxicity of cisplatin. However, other modulators of its activity could be of interest for further studies in head and neck cancer patients.

Adult↗

PubMed2002

Comparison of the efficacy of two different dosage dacarbazine-based regimens and two regimens without dacarbazine in metastatic melanoma: a single-centre randomized four-arm study.

The aim of this randomized four-arm phase III study was to evaluate whether there is a difference in activity between regimens containing dacarbazine and regimens without dacarbazine in metastatic melanoma, whether there is a dose-effect relationship for dacarbazine, and whether non-dacarbazine-containing aggressive regimens are in any way superior to non-aggressive ones. A total of 219 patients with metastatic cutaneous melanoma were included in this study; 196 of them were evaluable for activity. The patients were randomized into four treatment arms: arm A (standard dose dacarbazine arm), vincristine 1.4 mg/m2 on day 1, carmustine (BCNU) 60 mg/m2 on day 1, and dacarbazine 300 mg/m2 per 24 h on days 2-5; arm B (high-dose dacarbazine arm), vincristine and BCNU as in arm A and dacarbazine 600 mg/m2 per 24 h on days 2-5; arm C ('aggressive' regimen without dacarbazine), vindesine 3 mg/m2 on day 1, bleomycin 7 mg/m2 per 24 h on days 1-4, and cisplatin 30 mg/m2 per 24 h on days 5-8; arm D ('non-aggressive' regimen without dacarbazine), BCNU 100 mg/m2 on day 1 and procarbazine 90 mg/m2 per 24 h on days 1-10. The four arms were well balanced with regard to patient- and disease-related characteristics. On an intend-to-treat basis, the response rate was 11 out of 49 (22%) in arm A, nine out of 47 (19%) in arm B, 16 out of 63 (25%) in arm C and nine out of 60 (15%) in arm D. There was a large overlap between the 95% confidence intervals and no significant differences in the response rates between the four arms. Median survival in the four treatment arms was 4, 5, 6 and 4 months, respectively, again with no significant differences. Median survival for responders (8, 11, 10 and 13 months, respectively) in all four arms was significantly longer than in non-responders (4, 3, 5 and 4 months, respectively). Arms A, B and C were significantly more toxic compared with arm D, which was for all practical purposes devoid of toxicities. The efficacy of all four regimens thus appeared comparable both in terms of response rate and survival. Responders in all four arms achieved a survival benefit. There does not seem to be a dose-effect relationship for dacarbazine in metastatic melanoma. Chemotherapy from arm D, might be well suited for 'fragile' or elderly patients due to the lack of toxicity.

Adult↗

PubMed2002

Epidemiology of end-stage renal disease and current status of hemodialysis in Yugoslavia.

Maintenance hemodialysis (HD) in Yugoslavia started in the sixties and followed the dialysis trends in the Western Europe. However, in the last decade the development of renal replacement therapy (RRT) slowed down. In this report the epidemiology of ESRD from 1997-1999 and the survey of the status of HD treatment in Yugoslavia in 1999 are presented. Epidemiological data are obtained by the annual center questionnaires (response rate: 92.6 -94.2%). The survey of HD status is based on a specific questionnaire and covered 2108 patients (65%). At the end of 1999 there were 56 RRT centers in Yugoslavia treating 3939 patients: 3232 (82%) patients by HD, 248 (6.3%) by peritoneal dialysis, and 459 (11.7%) living with transplanted kidney. In a three year period, incidence of ESRD ranged from 108-128 pmp, point prevalence from 435-463 pmp and mortality rate from 20.7-17.9. Numerous refugee patients were treated over the last 10 years. Main causes of ESRD were glomerulonephritis (30%); Balkan nephropathy represented 11% and diabetic nephropathy 7% of all primary renal diseases. Cardiovascular and cerebrovascular diseases were the most common causes of death of RRT patients. Most centers are overcrowded and HD machines are worn out. Mean Kt/V was 1.19+/-0.08, mean URR% 58.8+/-7.4. The shortage of drugs prevented adequate management: 83% of HD patients had hemoglobin level less than 100 g/L but only 10.3 -17.8% were treated with rHuEpo; 64.5% of patients had phosphate levels higher than 1.7 mmol/L but only 33.5% used phosphate binders; 47% of patients had hypertension despite the antihypertensive therapy. The prevalence of hepatitis B remained unchanged (about 14%) in HD population during the last three years, but the prevalence of anti-HCV positive patients decreased (31-23%). In conclusion, there is a well developed dialysis service in Yugoslavia but insufficient conditions for adequate treatment.

Balkan Nephropathy↗

PubMed2002

Chemoembolization for liver metastases from colorectal carcinoma: risk or a benefit.

Results from clinical trials do not allow definitive conclusions about the role of chemoembolization (ChE) in the treatment of colorectal cancer (CRC) liver metastases. The aim of present phase II study was to investigate toxicity and efficacy of ChE for patients, with unresectable colorectal liver metastases after failure of 5-FU based chemotherapy. Secondary endpoint was clinical benefit measurement. Eleven patients were enrolled in first stage (two-stage Simon design), 2 males/9 females, median age 60 (46-71). Performance status was I in 8 patients and II in 3 patients. All patients had radical surgery, 7 of them adjuvant chemotherapy and 4 systemic chemotherapy. The ChE regimen consisted of an injection of iodinated oil Lipiodol with mitomycin C (3 mg/ml). Repeated treatments were performed at 9- to 12-week intervals. We applied 17 ChE (median 1/pts.). Clinical benefit was a composite of measurements of pain, ECOG performance status, weight and tumor fever. Study was stopped after first stage because non of the patients (pts) achieved objective response (RECIST). Stable disease occurred in 5 pts (45%). Median time to progression was 3 months (range 3-9 months). Median survival was 9 months (range 4-16 months). A decrease of the baseline carcinoembryonic antigen level occurred in 0% of the cases. Clinical benefit was recorded in one patient. Common toxicity included a "postembolization syndrome," which consisted of fever, pain in the right upper quadrant, nausea, and vomiting. Grades 3-4 toxicity (NCI-CTC) followed transaminases 6/11, LDH 4/11. In addition, a drop in F V levels was noted in 5 pts, F VII in 9, F IX in 2 and F X in 10 pts. Decrease in At III levels occurred in 6 pts and FDP appeared in one. Thus, The ChE as performed in the present study did not appear to bring any benefit; furthermore, significant liver toxicity compromises the safety of such procedure.

Aged↗

PubMed2001

Survival advantage for carboplatin substituting cisplatin in combination with vindesine and mitomycin C for stage IIIB and IV squamous-cell bronchogenic carcinoma: a randomized phase III study.

This communication represents the definitive report of a randomized phase III study comparing cisplatin and carboplatin, in combination with vindesine and mitomycin C in stage IIIB and IV squamous-cell bronchogenic carcinoma. A total of 221 patients entered the study and were randomized into two arms. Of these, 114 patients (109 evaluable for activity) were randomized to arm A, receiving cisplatin 120 mg/m(2), mitomycin C 8 mg/m(2) and vindesine 3 mg/m(2) per cycle; 107 patients (101 evaluable for activity) were randomized to arm B receiving carboplatin 500 mg/m(2) with the same doses of mitomycin C and vindesine per cycle. Patients with progressive disease (PD) were excluded from the study after the 2nd cycle, and those with stable disease (SD), partial response (PR) and complete response (CR) received six cycles of chemotherapy (or less in case of early progression). Patients were stratified according to the clinical stage (IIIB vs. IV), performance status (0+1 vs. 2+3) and tumor histological grade (I+II vs. III). In the cisplatin arm two patients (1.9%) achieved a CR, 38 (34.9%) a PR, 45 (41.2%) a SD and 24 (22.0%) had PD; the overall response rate was 40/109 (36.8%). In the carboplatin arm five patients (5.0%) achieved a CR, 31 (30.7%) a PR, 40 (39.6%) a SD, and 25 (24.7%) had PD; the overall response rate was 36/101 (35.7%). No statistically significant difference in response rate was present between the two arms, and the response rate was not influenced by performance status, histological grade or clinical stage. The Kaplan-Meyers curves displayed a significant advantage both for time to progression (P=0.005) and overall survival (P=0.008) for patients in the carboplatin arm. The advantage for patients receiving carboplatin instead of cisplatin appeared evident in univariate setting for patients with a good performance status and clinical stage IV, and occurred irrespectively of tumor histological grade; response duration and survival of responders was identical in the two arms. Patients achieving a stable disease survived longer in the carboplatin than in the cisplatin arm (P=0.012). Thus, substitution of cisplatin by carboplatin in the combination chemotherapy regimen, although more hematologically toxic (but less emetogenic) resulted in a similar response rate, but a significantly longer time to progression and overall survival.

Adult↗

PubMed2001

Vinblastin-carboplatin for metastatic cutaneous melanoma as first-line chemotherapy and in dacarbazine failures: a single-center study.

First-line treatments of metastatic melanoma are usually decarbazine (DTIC) and/or alpha-interferon based, with response rates in the range of at most 20-30%. In this study, initiated, in fact, by a temporary DTIC shortage in the country, we have assessed the efficacy and toxicity of a vinblastine-carboplatin regimen for metastatic melanoma. The regimen was subsequently applied in two cohorts of patients: a chemotherapy-naive one and in DTIC failures (because the regimen was claimed non-cross-resistant). The regimen contained 6 mg/m2 vinblastine on d 1 and 450 mg/m2 carboplatin on d 1 for 3 wk. In the chemotherapy-naïve cohort, 50 patients were included, 29 males and 21 females, median age 54 yr (range: 33-68), performance status 0+1 for 26 patients and 2+3 for 24 patients. Forty-eight patients were evaluable for activity. The response was the following: complete response (CR), 1/48 (2%); partial response (PR), 13/48 (27%); stable disease (SD), 20/48 (42%); progressive disease (PD), 14/48 (29%). The overall response rate was 14/48 (29%). The median response duration was 7 mo (range: 3-14); the median time to progression was 4 mo (range: 2-14). Toxicity included granulocytopenia and thrombocytopenia grade IV in 3/50 patients and nausea grade II in 8/50 patients. In the DTIC-failures cohort, 58 patients were included, 38 males and 20 females, median age 51 yr (range: 20-65), performance status 0+1 for 25 patients and 2+3 for 33 patients. All 58 patients were evaluable for activity. The response was the following: CR 3/58 (5%), PR 4/58 (7%), SD 10/58 (17%), PD 41/58 (71%). The overall response rate was 7/58 (12%). The median response duration was 11 mo (range: 3-24); the median time to progression was 4 mo (range: 2-24). Toxicities included granulocytopenia grade IV in 4/58 patients and nausea grade II in 4/58 patients. Thus, despite the fact that the regimen achieved a response rate comparable to DTIC in a first-line setting, the lack of cross-resistance did not prevent it from being of limited activity in DTIC failures, although, even in this group, several long-lasting responses and stabilizations were noted.

Adult↗

PubMed2001

Therapeutic implications of the kinetics of immunomodulation during single or combined treatment of melanoma patients with dacarbazine and interferon-alpha.

The therapy of metastatic melanoma has not given satisfactory results. Single chemo- or immunotherapeutic agents in the adjuvant setting or combined chemoimmunotherapy for metastatic disease have generally been evaluated only in terms of clinical benefit. Considering that dacarbazine (DTIC) and interferon-alpha (IFN-alpha) are among the most frequently used agents in the treatment of melanoma, the aim of this study was to evaluate the kinetics of immunological changes during adjuvant treatment of melanoma patients with DTIC or with IFN-alpha monotherapy, as well as by their combination in metastatic disease. The evaluated immunological parameters showed significant early increase in the activity of NK (natural killer) cells, CD4/CD8 ratio, CD4+ T cell number in patients treated with combined chemoimmunotherapy and an increase in expression of the early activation antigen CD38 on CD8+ cytotoxic T cells, both, in patients treated with combined chemoimmunotherapy and with IFN-alpha alone, while, no significant change in any one parameter was detected in the group of patients receiving DTIC. The kinetics of the observed immunological changes, restricted to combined chemoimmunotherapy, indicate that the engagement of antitumor immune response appears early but is short-lived and that this favorable effect should be augmented and prolonged by the timely introduction of additional immunomodulating agents.

ADP-ribosyl Cyclase↗

PubMed2000

Eight-hour infusion versus bolus injection of doxorubicin in the EAP regimen in patients with advanced gastric cancer: a prospective randomised trial.

BACKGROUND: Doxorubicin (40 mg/m2/cycle), etoposide (360 mg/m2/cycle) and cisplatin (80 mg/m2/cycle) comprise an efficient regimen in patients with advanced gastric cancer (AGC). However, its excessive hematological toxicity led doctors to avoid using the combination. Doxorubicin is the main cause of myelotoxicity in the EAP regimen. The aim of this study was to compare an eight-hour infusion of doxorubicin (arm A) with intravenous injection of doxorubicin (arm B) in the EAP regimen with respect to toxicity, objective responses, time to progression (TTP) and survival in patients with AGC. PATIENTS AND METHODS: One-hundred twenty chemotherapy-naïve patients with measurable AGC were randomised between September 1994 and August 1998. Sixty patients in arm A and sixty patients in arm B were considered as fully evaluable. The arms were well balanced for age, sex distribution, previous therapy, histological grade and performance status. One-hundred eighty cycles were applied in arm A (median 2) and 201 in arm B (median 4). RESULTS: No difference was detected (P = 0.28) in the response rate of arm A 20% (CR 3; PR 9; 95% CI: 10-30) and B 28% (CR 3; PR 14; 95% CI: 17-40). But there was a significant difference in PD (P = 0.005) between arm A (51%) and arm B (36%). TTP (P = 0.01) and survival (P = 0.02) analyses detected an advantage for arm B vs. arm A. Grades 3-4 toxicity were as follows (arms A%/B%): anemia 8/10, leukopenia 24/26, thrombocytopenia 6/16 (significance, P = 0.05), nausea/vomiting 5/8, diarrhea 6/2, mucositis 8/5. Apart from the trombocytopenia, there was no significant difference in toxicity grades 3-4 between the two arms. Four treatment-related deaths occurred, two in each arm. CONCLUSIONS: Bolus injection of doxorubicin is superior to eight-hour doxorubicin infusion in the EAP regimen in terms of survival, TTP and PD without being significantly more toxic.

Adult↗

PubMed2000

Circulating immune complexes in advanced Hodgkin's disease: qualitative analysis and prognostic significance.

The level of circulating immune complexes (CIC) may be a reflection of the underlying malignancy and appears to be related to the stage of disease, tumor burden and prognosis. Prognostic factors at diagnosis, clinical response, survival and CIC were analyzed in 89 patients with Hodgkin's disease. All patients were newly diagnosed, in advanced stage and treated with MOPP regimen. The median follow-up was 41 months. CIC were estimated by the polyethylene glycol precipitation test. The median age was 40 years and 52% were under the age of 45. Nodular sclerosis and mixed cellularity were the most common histologies, 36 and 35% respectively. "B" symptoms were present in 65%, bulky disease in 29% and bone marrow involvement in 4% of the total. The erythrocyte sedimentation rate (ESR) was over 30 in 72% of patients and 27% had one or two extranodal localizations. Complete remission (CR) was obtained in 69 patients (77%). The only factor influencing the CR rate was the number of extranodal localizations (p<0.05). The ten-year relapse-free survival (RFS) and overall survival (OS) were 63 and 83%, respectively. RFS was adversely influenced by lymphocyte depletion histology (p=0.009) and by performance status over 1 (p=0.003). Elevated CIC levels were detected in 58% of the total. Patients with ESR over 30 had significantly higher values of CIC (p<0.05). Qualitative analysis of the CIC showed high levels of positivity to immunoglobulin G and M. C-reactive protein (CRP) was identified in 42% of all samples. CRP is an acute phase protein which shows conformational similarity to the immunoglobulin molecule. There were no significant correlations between levels of CIC and the other prognostic factors. Survival was not influenced by the CIC level.

Adult↗

PubMed1999

Positive serology for Lyme disease borrelias in primary cutaneous B-cell lymphoma: a study in 22 patients; is it a fortuitous finding?

BACKGROUND: The historical association of acrodermatitis chronica atrophicans (ACA), now known to be a late manifestation of Lyme disease caused by Borrelia afzelii, with cutaneous lymphoma, and several small series of PCBCL with positive Lyme disease borrelial serology initiated a study of this association. Material and methods In the last 9 years, 30 patients with PCBCL have been observed and followed, 22 of them were tested for borrelial serology. The control group consisted of 85 patients with NHL (10 cutaneous T-cell, 25 extranodal B-cell non-PCBCL, 50 nodal B-cell), 30 patients with breast cancer and 60 blood donors. The screening tests were two different ELISA tests for B. burgdorferi sensu lato and sensu stricto, and reactive sera were further tested with the ELISA test for B. garinii, a Western blot (WB) test for Swiss Borrelia strains and a WB test for Bavarian Borrelia strains, since an immunoblot made with local strains was not available. Studies with a differential WB test for B. burgdorferi sensu stricto, B. garinii and B. afzelii was performed afterwards, as well as serological studies ruling out cross-reactions with Leptospiras and Treponema. RESULTS: Fifteen of 22 patients with PCBCL were positive on the screening tests, three of them falsely. Thus, the incidence of positive borrelial serology was 12/22 (55 per cent) in the PCBCL group. No positives were detected in the cutaneous T-cell lymphoma group; 2/25 patients (8 per cent) were positive in the extranodal B-cell NHL group (the localizations being vestibulum nasi and oral cavity), 2/50 (4 per cent) were positive in the nodal B-cell NHL group, 2/30 (7 per cent) in the breast cancer group and 2/60 (3 per cent) in the blood donor group. The cumulative incidence in the control groups was 8/175 (4,6 per cent). The incidence was significantly higher in PCBCL patients as compared to each of the control groups, p value ranging from 0.004 to <0.0001. Two positive patients had ACA, one arthritis. Borrelia afzelii was most often implied for positive serology in the differential WB. No cross-reactions with Treponema and the Leptospiras were documented. CONCLUSION: In conclusion there appears to be a clustering of positive serology for Lyme disease Borrelias in PCBCL patients possibly related to an ethiopathogenic relationship. Mechanisms of Borrelia escape from immunosurveillance mechanisms, persistence of both their mitogenic and antigenic stimuli for B-cells, and SALT formation may be involved in the pathogenesis of a subset of PCBCL.

Acrodermatitis↗

PubMed1999

The role of stable disease in objective response assessment and its impact on survival in advanced colorectal cancer: is "stable disease" a homogenous response category?

Stable disease is a category which is not included in the evaluation of the overall treatment response rate. In many studies with a response rate below 20%, chemotherapy almost doubles the survival of patients. In the most chemotherapy trials with advanced colorectal cancer patients, about 30-50% had stable disease. Despite belonging to the same category of therapy response, some patients with stable disease have achieved symptom improvement, but some have not. The aim of the study was to investigate whether the stabilization of the disease with clinical benefit is associated with benefit in survival. A total of 99 patients with advanced colorectal cancer were treated with carboplatin (80 mg/m2, day 1-7), 5-FU (750 mg/m2, day 1-5), leucovorin (100 mg/m2, day 1-5) every 4 weeks. After 4 courses, in the case of stable disease (SD), the patients were stratified according to clinical benefit achievement in: Group A--patients with clinical benefit who continued with chemotherapy until 8 cycles or until disease progression; group B--patients without clinical benefit in whom chemotherapy was stopped after 4 cycles. Clinical benefit was a composite of assessment of pain, ECOG performance status, weight and temperature. Clinical benefit required a sustained improvement in at least one parameter without worsening in any other. Of 97 evaluable patients 48 achieved stable disease. Of 22 pts. with SD clinical benefit performance status improvement was recorded in 17, pain relief in 14, improvement in body weight in 14 and temperature disappearance in 8 pts. Of 26 pts. with SD without clinical benefit, 7 were asymptomatic from beginning of the chemotherapy. No difference was detected in the survival between responders and SD clinical benefit pts. (p = 0.24), but there was significant difference between responders and SD pts. without clinical benefit (p = 0.0004). SD clinical benefit pts. had significant difference in survival in comparison to pts. with progressive disease (p = 5.1 x 10(-6)). The results of our study indicate that under category "stable disease" there are two different subpopulations of patients with quite different symptom response to chemotherapy, different time to progression and possible different survival.

Adenocarcinoma↗

PubMed1999

The absence of correlation between immunoregulatory T cells and induced lymphoproliferative response in treated B-chronic lymphocytic leukemia patients.

BACKGROUND: Many data suggest T cell functional impairment in B-cell chronic lymphocytic leukemia (B-CLL). The mechanism responsible for this phenomenon is still unresolved. METHODS: In 88 B-CLL patients (RAI II-IV) the relationship between immunoregulatory T cells and PHA induced lymphoproliferative response (LPR) was analysed before and after the therapy. The number of peripheral blood CD3+, CD4+ and CD8+ T lymphocytes was determined by indirect immunofluorescence assay using monoclonal antibodies. LPR was estimated in whole blood culture method. RESULTS: The absolute number of CD3+, CD4+ and CD8+ cells in untreated CLL patients was much higher than in healthy controls (n = 26), but the percentages of these subpopulations, CD4/CD8 ratio and LPR to PHA were significantly (p < 0.00001) decreased. The chemotherapy induced a significant rise of CD3+ and CD4+ percentages (p < 0.006 < p < 0.022 respectively) in comparison to baseline levels, but their levels remained significantly (p < 0.00001) lower than the controls. The CD4/CD8 ratio was also elevated after the therapy (p < 0.048) but remained below the normal value as well. The absolute number of CD3+ and CD4+ T cells were normalized after treatment, while the CD8+ cells were still higher (p < 0.044) than controls. The increase of LPR has been registered after treatment, but it failed to reach the control values. We could not find any correlation between the number of immunoregulatory T cells and induced LPR (r = 0.07, for CD4+; r = 0.09 for CD8+ cells). CONCLUSIONS: These data indicate some profound lymphoid cell defect in CLL patients affecting CD8+ proliferation as well as LPR.

Adolescent↗

PubMed1999

Comparison of two non-anthracycline-containing regimens for elderly patients with diffuse large-cell non Hodgkin's lymphoma--possible pitfalls in results reporting and interpretation.

Age over 65 years is a risk factor per se for doxorubicin administration, and coexisting diseases pose additional problems. There is still controversy whether chemotherapy regimens for elderly patients with aggressive NHL should be full-dose doxorubicin containing or whether development of non-anthracycline containing regimens is warranted. In this prospective study, 47 patients aged over 65 years with diffuse large cell NHL clinical Stage I/IE bulky-IV and no other initial exclusion criteria were randomized to receive either BCNU 120 mg/m2 d. l, VP 16 60 mg/in2 d.2-4, procarbazine 85 mg/m2 d. 2-8 (arm A, 27 patients) or mitoxantrone 6 mg/m2 d. l. with VP16 and procarbazine in the same dosage and schedule (Arm B, 20 patients). Partial responders received additional irradiation treatment if feasible. Arms were well balanced according to age, sex, clinical stage and performance status. Ten patients from arm A and 13 from arm B had PS 2 or 3; 14 patients from arm A and 8 from arm B had clinically significant antecedent and/or concomitant disease (SACD: cardiac, vascular, cerebrovascular, neurological, renal or other). On the intent-to-treat basis, the results were the following. ARM A: median number of cycles 3 (range 1--6); early death 3 patients; 16/27 responses (59%), 7 complete (30%). ARM B: median number of cycles 3 (range 1-6); early death 4 patients; 12/20 responses (60%), 3 complete (15%). There was no difference either in response rate or survival between the two arms, and pooled results from the two arms displayed a plateau on the survival curve from the 20-th month onwards on the probability level of 0.40. Clinical stage of NHL, bulky disease, age and sex did not influence survival. Initial performance status did influence survival at the significance level of p = 0.045. Although presence of SACD did not influence initial performance status, it had a strong negative impact on survival p = 0.0004). The results point to the existence of two prognostic categories of elderly patients with large cell NHL, one with a poor survival, the other achieving a significant response rate and relapse free survival. Comorbidity (SACD) apparently accounts for the poor survival in a subpopulation of elderly patients. Clinical trials with elderly patients with NHL with PS 0 or 1 and no serious coexisting disease as inclusion criteria, analyzed on an evaluable patients basis, target only to a prognostically better subpopulation among these patients.

Aged↗

PubMed1999

Epirubicin 150 mg/m2-cisplatin versus epirubicin 180 mg/m2-cisplatin for advanced soft tissue sarcoma.

We have previously reported the superiority of the epirubicin 180 mg/m2-cisplatin combination over single drug epirubicin 180 mg/m2 for advanced soft tissue sarcoma both in terms of response (54% vs. 29%, p = 0.025) and survival (p = 0.001). The aim of the present study was to establish whether decreasing the dosage of epirubicin to 150 mg/m2 would result in the same activity but with less hematological toxicity. One hundred fifty-nine patients with advanced soft tissue sarcoma were randomized for either epirubicin 150 mg/m2-cisplatin 120 mg/m2 (group A) or epirubicin 180 mg/m2-cisplatin 120 mg/m2 (group B). The results were as follows: group A: 79 patients were evaluated. Overall response rate was 24/79 (30%) (95% CI 21-41%). Median survival was 11 months and probability of survival at 1 year was 0.46. Grade IV granulocytopenia was present in 111/274 cycles and febrile neutropenia in 22/274. Group B: 73 patients were evaluated. The overall response rate was 39/73 (53%), (95% CI 42-64%). Median survival was 14 months and probability of survival at 1 year was 0.58. Grade IV granulocytopenia was present in 136/295 cycles and febrile neutropenia in 30/295. The differences were as follows: for overall response rate p = 0.004; power (for p = 0.05) 85%; for survival p = 0.09; for grade IV granulocytopenia p = 0.3; and for febrile neutropenia p = 0.61. A survival advantage (p = 0.043) was evident for patients randomized to group B and with performance status 0 or 1 compared with similar patients from group A. A plateau-like formation on the probability level of 0.26 on the survival curve started from month 26 onwards. In conclusion, both regimens share the same toxicity but epirubicin 180 mg/m2-cisplatin seems more active in soft tissue sarcoma, possibly indicating a breakthrough for activity between an epirubicin dosage of 150 mg/m2 and 180 mg/m2 in combination with cisplatin. The superiority of the epirubicin 180 mg/m2-cisplatin regimen appears evident both in terms of response and survival.

Adolescent↗

PubMed1997

A controversial issue: could a watch-and-wait policy for patients with non-Hodgkin's lymphoma clinical stage I or IE with no lymphoma left following diagnostic surgery be justified? Results of a single centre study.

BACKGROUND: A subset of patients with non-Hodgkin's lymphoma (NHL) with clinical stage I or IE at presentation is left without other NHL localizations following surgery performed for diagnostic histology, and thus without any target lesion to judge the immediate effectiveness of immediately applied additional treatment modalities. MATERIAL AND METHODS: Since 1988 we have adopted in this single centre, prospective non-randomized study, a watch-and-wait policy for such patients, who in addition had to have non-bulky disease, normal LDH levels, no 'B' symptoms and no Burkitt, lymphoblastic and cutaneous T-cell histology. Up to 1993 we have observed 50 consecutive cases. Patients were regularly followed with the endpoint to determine the relapse-free interval and overall survival. NHL relapses were treated, either with locoregional radiotherapy, or with chemotherapy, or both. RESULTS: The median observation time is at the moment 53.5+ months (range 6-106+). The initial NHL localizations were: a solitary cervical or auxillary lymph node in 18 patients, inguinal or scarpal lymph node in eight, tonsil in 12 and skin/subcutis in 12 (B-cell NHL only for skin/subcutis). Nine patients had low, 15 intermediate, and 26 high-grade histology. Within the observation period NHL relapses occurred in 10/50 patients (20 per cent). At the moment 46/50 patients (92 per cent) are alive and NHL free. The estimated 9-year freedom from relapse is 79 per cent and overall survival 92 per cent, and for 41 patients with intermediate/high-grade histologies 80 per cent and 95 per cent respectively. CONCLUSION: It seems that a proportion of the very selected subgroup of patients with stage I of IE NHL and absolutely no NHL left following diagnostic surgery, with additional criteria as described in this study can achieve a substantial freedom from relapse and overall survival rate without immediate additional therapeutic procedures following diagnosis of NHL, but no prognostic factors predicting this outcome seem yet available.

Adult↗

PubMed1997

Randomised study of high-dose epirubicin versus high-dose epirubicin-cisplatin chemotherapy for advanced soft tissue sarcoma.

A randomised study was started in chemotherapy-naive patients with advanced soft tissue sarcomas who received either epirubicin 60 mg/m2/24 h (total dose for cycle 180 mg/m2) days 1, 2 and 3, (group A) or epirubicin 60 mg/m2/24 h days 1, 2 and 3 and cisplatin 30 mg/m2/24 h days 2, 3, 4 and 5 (group B). The maximal number of cycles foreseen in both groups was eight. Cardiotoxicity of the regimens was monitored by serial LVEF determinations. 106 patients entered this study, 50 (45 evaluable for activity) randomised to group A, and 56 (54 evaluable for activity) to group B. The groups were well balanced for age, sex, performance status and histological type. In group A, there was 1 complete response (CR) and 12 partial responses (PR), the overall response being 13/45 (29%); in group B, there were 7 CRs and 22 PRs, the overall response being 29/54 (54%). The difference between the overall response was statistically significant (chi 2 = 6.19, P < 0.025). The epirubicin-cisplatin regimen was found to be more toxic for platelets and more emetogenic, but cardiotoxicity, either acute or cumulative, was not found to be a major problem in both groups. However, a complete responder receiving a cumulative epirubicin dose of 1440 mg/m2 died from congestive heart failure after a disease-free interval of 27 months. The high response in group B could be the result of the synergism between high-dose epirubicin and cisplatin in patients with advanced soft tissue sarcomas.

Adult↗

PubMed1997

Randomized study of zorubicin versus zorubicin-cisplatin in undifferentiated carcinoma of the nasopharynx (UCNT)

BACKGROUND: The most active chemotherapy regimens in UCNT were those combining anthracyclines (doxorubicin or epirubicin) and cisplatin. Our previous pilot study on 37 patients treated with the zorubicin-cisplatin combination with a RR of 67% and literature data about other anthracyclines such as epirubicin achieving a response rate of over 50% were the basis of this randomized study comparing efficacy and toxicity of the combination vs. zorubicin as monotherapy. PATIENTS AND METHODS: A total of 80 patients entered the study. The diagnosis of UCNT was confirmed by two independent pathologists. All patients had their primary tumors in the nasopharynx. The patients were randomized in two groups: group A (zorubicin 325 mg/m2, day 1), and group B (zorubicin 250 mg/m2, day 1 and cisplatin 30 mg/m2, days 2-5). The inter-cycle interval was four weeks. The two groups were well balanced according to sex, age, stage Ho and TNM stage. RESULTS: Group A: 40 patients included, 34/40 evaluable for activity. Activity on evaluable patient basis: CR 4/34 (11.75%), PR 4/34, SD 14/34, PD 12/34, response rate 8/34 (23.5%); response rate on intent to treat basis 8/40 (20%). TOXICITY: granulocytopenia grade 3-4 6/40, thrombocytopenia grade 3-4 2/40, no febrile neutropenias, nausea/vomiting any grade 3/40, cardiac toxicity any grade (rhythm) 3/40 other toxicities minor or absent. Group B: 40 patients included, 36/40 evaluable for activity. Activity on evaluable patient basis: CR 10/36 (27.78%), PR 17/36, SD 3/36, PD 6/36, response rate 27/36 (75%); response rate on intent to treat basis 27/40 (67.5%). TOXICITY: granulocytopenia grade 3-4 10/40, thrombocytopenia grade 3-4 8/40, two febrile neutropenias, nausea/vomiting any grade 13/40, other toxicities mild or absent. Of the group of patients achieving a CR, four relapsed following 7, 11, 22 and 23 months, one was lost to follow-up, one died after six months from fulminant hepatitis B and eight are in complete remission lasting for 30+ to 66+ months. Following CR achievement none received any consolidation radiotherapy, and the projected five years of freedom from relapse for complete responders is about 60%. CONCLUSION: Zorubicin is an effective drug in UCNT and its combination with cisplatin has a significant activity and an acceptable toxicity.

Adolescent↗

PubMed1997

Richter syndrome with emphasis on large-cell non-Hodgkin lymphoma in previously unrecognized subclinical chronic lymphocytic leukemia.

The authors report seven cases of Richter's syndrome, i.e. of large-cell non-Hodgkin's lymphoma (NHL) arising in association with chronic lymphocytic leukemia (CLL). Six patients had the recently recognized variant of this syndrome, occurring in patients with previously undiagnosed subclinical CLL. All patients were treated with aggressive chemotherapy and a complete response of large cell NHL was achieved in 4/7. A complete response of NHL was observed in 3 out of 6, and a partial response in 2/6 patients with simultaneous occurrence of subclinical CLL and large cell NHL (response rate 5/6). Our findings might suggest that patients with Richter syndrome occurring in previously undiagnosed subclinical CLL could represent a better prognostic group in the overall population of patients with large cell NHL transformation of CLL.

Aged↗