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D Gavrilović

Publications and source records attributed to D Gavrilović.

9 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↗
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↗
PubMed1999

Expression of epidermal growth factor receptor in breast cancer, from early stages to advanced disease.

Epidermal growth factor receptor was determined in 106 newly diagnosed breast cancer patients, using the biochemical method. The group consisted of 58 patients in stage I-II, and 48 patients in stage III-IV. Although a significant inverse correlation was found between EGF-R status, and ER or PR status, quantitative content of EGF-R did not correlate either with quantitative ER, or PR levels. The ER/PR content was similar in all clinical stages, suggesting their stability during the clinical course of the disease. EGF-R content was significantly higher in stage IV, compared to stage I, while intermediate clinical stages and all substages did not differ according to the EGF-R content. EGF-R was confirmed as a weak prognostic factor within clinical stages. However, in a whole group, the overall survival was significantly better in patients whose tumors EGF-R content was lower than 26 fmol/mg, compared to those with higher ERF-R content. EGF-R content was highly predictive for the response to systemic endocrine treatment, in metastatic breast cancer patients. In locally advanced breast cancer a trend towards higher levels of EGF-R was found in inflammatory breast cancers, compared to non-inflammatory ones. Slightly higher levels were found in responders to local non-endocrine primary treatments (radiotherapy with or without chemotherapy), compared to non-responders, suggesting the possible predictive role of EGF-R for the response to such treatments. Our results emphasized the usefulness of quantitative receptor determination suggesting the relative stability of EGF-R content during the clinical course of breast cancer, its independence from ER, its significant predictive and weak prognostic values, and a possible correlation with the aggressiveness of the disease, and response to non-endocrine treatments.

Aged↗
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↗
PubMedDate not supplied

[Role of radiotherapy in combined therapy of soft tissue sarcoma in children and adolescents].

Over last decades with modern approach to combined treatment of soft tissue sarcoma in children and adolescents, with effective systemic chemotherapy and adequate local control most frequently with conservative surgery and radiotherapy, or radiotherapy alone, results of treatment from 20% of a three-year overall survival to 75% were improved significantly. Nevertheless, combined treatment involves risk of acute radiation reactions and late side effects, so there is a need for precise radiotherapy planning with optimal schedule of fractionating, adequate radiation volume and optimal tumour dose. The purpose of our study was to evaluate the results of combined treatment of soft tissue sarcoma, role of radiotherapy in local control use of the optimal tumour dose and assessment of acute radiation reactions in an examined group of patients. A retrospective clinical study involved 47 patients treated with radiotherapy at the Institute of Oncology and Radiology of Serbia over the period from 1990 to 1997. The most frequent tumour sites were the head and neck and the extremities. According to the IRS classification most patients were in CS III (21 patients). Forty patients had histological type--Rhabdomyosarcoma (Table 1). All patients were treated with chemotherapy, and local therapy were surgery and radiotherapy or radiotherapy alone. Thirty one patients were operated on. All 47 patients were treated with radiotherapy; in 37 patients as primary treatment and in 10 patients as therapy for local relapse. Radiotherapy was planned according to tumour size, tumour site, age of the patient and type of surgery. Tumour dose from 45 Gy to 60 Gy was given in cases with a residual tumour. Lower tumour doses were used in cases of postoperative microscopic disease, in certain cases of local relapse treatment or when the size of residual tumour and patient's age allowed no delivery of higher tumour doses. Standard fractionating regimen was given to all patients, with daily fractions from 150 cGy to 214 cGy, five times per week. The majority of patients (24) were treated on Linear Accelerator machine with X photons of 10 MeV energy and with X photons of 6 MeV energy (13 patients) (Table 2). Statistical data processing was made by the following methods: Kaplan-Meier for survival rate and Long-rang and Wilcox test for assessment of the statistical significance in survival difference. In our group of patients treated over the period from 1990 to 1997 a three-year overall survival was 59.15%, and disease free survival was 46.68% (Figure 1). There were 21 patients (44.7%) without signs of the disease, 12 patients had a local disease (25.5%), 9 patients had both local and metastatic disease (19.1%) and 5 patients had only metastatic disease (10.50%). In the group of 47 patients who received radiotherapy, 24 patients received a tumour dose from 45 Gy to 60 Gy and 23 patients a tumour dose from 32 Gy to 45 Gy. The group of patients treated without tumour dose more than 45 Gy had a significantly better overall survival rate (p = 0.002) (Figure 2). Although the obtained results are in agreement with data from literature, a critical analysis is necessary. Namely, in addition to the group irradiated with a tumour dose from 32 Gy to 45 Gy, because of the postoperative microscopic disease, certain number of patients was irradiated with a "lower" dose because of an objective impossibility to administer a "higher" dose or this dose was planned for palliative reasons. The tumour dose of 45 Gy was delivered to 6 of 10 patients treated for local relapse. The tumour dose of 45 Gy was also used in four patients in CS IV, in two subjects for local control and in two as a palliative treatment. Seven patients in CS III received a tumour dose of 45 Gy, because the age of children, tumour site and tumour size permitted no higher tumour doses. That is when planning an adequate local therapy one must have in mind the initial tumour size, type of administered systematic chemo

Adolescent↗