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Biomedical subjects

S Pavlovsky

Publications and source records attributed to S Pavlovsky.

At least 55 records · Page 3Linked to original sources

Comparison of two consecutive trials for treatment of childhood non-Hodgkin's lymphoma.

Two consecutive trials for the treatment of childhood non-Hodgkin's lymphoma were evaluated, carried out by the same cooperative groups. Group A: From June, 1973 to December, 1975, 50 evaluable patients under 16 years of age participated in a study that included vincristine and prednisone plus surgery and/or radiotherapy as induction. This was followed by 2400 rad of cranial radiotherapy plus 5 doses of intrathecal methotrexate-dexamethasone and anti-leukemia (6-mercaptopurine, methotrexate, cyclophosphamide) or anti-lymphoma (cyclophosphamide, vincristine, procarbazine, and prednisone) maintenance treatment. Group B: From January, 1976 to December, 1980, 55 evaluable patients participated in a consecutive study that added Adriamycin (doxorubicin) and cyclophosphamide to the former induction regimen. Central nervous system (CNS) prevention was performed with 5 doses of intrathecal methotrexate-dexamethasone. Maintenance treatment was the same. Prognostic factors as stage and primary site were comparable in both groups. A total of 33 (66%) of 50 children of Group A and 48 (87%) of 55 children of Group B achieved complete remission (P less than 0.005). Disease-free survival at 60 months was 27% in Group A and 49% in Group B; for Stage I-II, 30% in Group A and 85% in Group B (P less than 0.025); for Stage III-IV 28% in Group A and 36% in Group B (not significant). In Group A, 9.1% and in Group B, 8.3% had primary CNS relapse. Both maintenance schedules had the same relapse rate. It was concluded that: (1) the addition of Adriamycin and cyclophosphamide to vincristine-prednisone in Group B produces a higher rate of complete remission in Stage III-IV, a higher rate of disease-free survival in Stage I-II, and a higher survival rate in all stages; (2) CNS prevention with intrathecal methotrexate-dexamethasone is equally effective as cranial radiation plus intrathecal methotrexate-dexamethasone; and (3) anti-leukemia and anti-lymphoma maintenance are equally effective in the context of this study.

Adolescent↗

Multidisciplinary consideration of cancer therapy in Latin America.

A multidisciplinary approach to cancer control, diagnosis, pretreatment evaluation and particularly treatment requires cooperation among surgeons, internists, chemotherapists and radiotherapists. The best sequence of radiotherapy and chemotherapy in patients who need both treatments is essential to avoid interference between treatments or potentiation of the adverse toxic effects. Several features may interfere in the detection and delivery of the best treatment combination in patients with cancer in Latin American countries, compared to patients in more developed countries: (1) There are differences among countries in the percentages for certain cancer sites and stages of disease. (2) Most of the cancer incidence figures are originated in hospital-based registries and not population-based registries. (3) On many occasions the modality of treatment of an individual patient depends on which doctor the patient sees first--the physician, the surgeon, or the radiotherapist. (4) In many radiotherapy services the treatment capacity is outweighed by the great amount of cancer patients, and radiotherapy is used primarily for curative purposes. (5) A higher percentage of patients arrive with advanced incurable disease because of lack of the awareness of the significance of early signs and symptoms on the part of patients, relatives and even doctors. (6) Another frequent problem is the lack of communication, transportation and accommodations near the treatment center. Many patients come from long distances; these factors make adequate follow-up of patients difficult. (7) There is a lack of radiotherapy services and there are numerous non-functioning units due to break-downs. A collaborative cancer treatment research program was initiated in 1977 between Latin American cancer centers and U.S. centers. This program is coordinated by the Pan American Health Organization and U.S. National Cancer Institute. Most of the protocols include multiple modality treatment (surgery, radiotherapy, chemotherapy and immunotherapy). This program has shown that, good control clinical trials can be performed in multiple cancer centers in Latin America in spite of the problems mentioned above.

Combined Modality Therapy↗

A randomized trial of melphalan and prednisone versus melphalan, prednisone, cyclophosphamide, MeCCNU, and vincristine in untreated multiple myeloma.

In a randomized study with 234 previously untreated patients with multiple myeloma, 129 were treated with melphalan (8 mg/m2 perorally for four days) and prednisone (40 mg/m2 perorally for seven days, both every four weeks) and 105 with melphalan and prednisone at the same doses plus cyclophosphamide (600 mg/m2 intravenously every four weeks), MeCCNU (100 mg/m2 PO every eight weeks), and vincristine (MPCCV, 0.6 mg/m2 IV every four weeks). A total of 49 (38%) of the 129 patients treated with melphalan and prednisone (MP) and 48 (46%) of the 105 patients treated with MPCCV showed good response (GR) (P not significant); the overall response rates were 58% and 70%, respectively. Thirty-seven percent of the MP group and 39% of the MPCCV group remain alive at 48 months from first treatment (P not significant). The estimated 48-month survival from first treatment, according to different prognostic factors at diagnosis, in both groups was as follows: stage 1,56%; stage II, 46%, and stage III, 23% (I and II v III P less than .001). Survival at 48 months according to response was GR, 68%; partial response (PR), 33%; and null, 16% (GR v null, P less than .0005; GR v PR, P less than .0005). Survival according to renal function was 43% for a creatinine level less than 2 mg/100 mL and 27% for a creatine level greater than or equal to 2 mg/100 mL (P less than .0005). No significant difference has been found between the two treatment schedules in terms of response rate and survival time, in any stage of disease.

Antineoplastic Combined Chemotherapy Protocols↗

Alternating pulses of vincristine-prednisone with cytarabine-cyclophosphamide versus vincristine-prednisone in the maintenance therapy of acute lymphoblastic leukemia.

From January 1976 to December 1978, 347 children less than or equal to 15 years of age were entered in a collaborative controlled trial which included: induction (vincristine-daunorubicin-prednisone); intensification (cytarabine-cyclophosphamide); CNS prevention (intrathecal methotrexate-dexamethasone, three doses during induction and three weekly doses during the first month of maintenance, followed by one dose every 3 months for 48 months); and maintenance (6-mercaptopurine daily and methotrexate twice weekly with reinforcement pulse doses of either 1.5 mg/m2 X 1 of vincristine plus 40 mg/m2/day X 7 of prednisone [Arm A] or vincristine-prednisone alternating with 50 mg/m2 of cytarabine sc every 12 hours X 10 plus 600 mg/m2 X 1 of cyclophosphamide [Arm B]). Pulses were performed in both arms at 1, 2, 3, 4, and 6 months and every 3 months thereafter. Randomization was stratified according to age and initial wbc count. A total of 89% (310/347) of patients achieved complete remission. Duration of continuous complete remission was evaluated according to prognostic factor groups. At 5 years, 34.5% of patients with good prognosis, 24.8% with intermediate prognosis, and 12.8% with poor prognosis are in continuous complete remission. There is statistical difference between good versus poor prognosis (P less than 0.0005) and intermediate versus poor prognosis (P less than 0.025). Moreover, 5-year survival is 50.9%, 35.2%, and 18.2% in the good-, intermediate-, and poor-prognosis groups, respectively. Duration of continuous complete remission up to the first event (ie, bone marrow, CNS, or other extramedullary relapse, or death in complete remission), according to prognostic groups, did not differ in relation to reinforcement pulses (Arm A or B). We conclude that there was no benefit in alternating pulses of vincristine-prednisone with cyclophosphamide-cytarabine as used in this study.

Acute Disease↗

Vindesine, prednisone, and daunomycin in acute lymphoblastic leukemia in relapse.

Patients with resistant or recurrent acute lymphoblastic leukemia were treated with vindesine 3 mg/m2/IV weekly X 4, daunomycin 25 mg/m2/IV weekly X 4, and prednisone 40 mg/m2/PO daily X 28. Seventeen (44%) of 38 evaluable patients achieved complete remission. Fifty-one percent of 31 patients in first relapse achieved complete remission, while only one of five in second or third relapse and neither of two resistant to first induction achieved complete remission. The major toxicity was hematologic. The median duration of complete remission was only 6 weeks and median survival from start of the study, 3 months, with 22% patients remaining alive at 10 months. We conclude that the vindesine, prednisone, and daunomycin combination is no more effective than vincristine, prednisone, and daunomycin in achieving remission of relapsed acute lymphoblastic leukemia patients, and is more toxic than the latter regimen.

Adolescent↗

Evaluation of testicular function following long-term treatment for acute lymphoblastic leukemia.

A study of reproductive function was carried out in 31 patients following long-term treatment of acute lymphoblastic leukemia (mean: 4 1/12 years); 17 prepubertal; nine pubertal, and five adults. Spontaneous clinical pubertal development was observed in 4 of 17 prepubertal patients. Serum testosterone response to hCG was normal or increased in the nine prepubertal patients studied. Intratesticular testosterone concentration was normal in 11 out of 12 patients. Only two of 14 prepubertal patients had a reduced number of germ cells. Normal progress of spermatogenesis was seen in six out of seven pubertal patients and only moderate hypospermatogenesis with focal hyalinosis was found in the five adults. Two of them had normal sperm count and one fathered two children. In six out of 14 prepubertal patients unexpected early signs of pubertal stimulation were found. Serum gonadotrophins response to LH-RH was normal in most patients. Testicular infiltration of blastic cells was found in four of 26 biopsies, but only one of 23 patients was without clinical signs of testicular relapse. Computerized axial tomography was normal in 10 out of 13 patients. Bone age was significantly below chronological age in four out of 15 patients. This study suggests that the gonad is moderately injured by long-term antileukemic therapy. In addition, microscopic testicular infiltration is not frequent in subjects without testicular enlargement.

Adolescent↗

Daunorubicin, vincristine, and prednisone for remission induction in patients with acute lymphoblastic leukemia in relapse.

Patients with recurrent acute lymphoblastic leukemia were treated with daunorubicin (40 mg/m2/week X 4), vincristine (1.5 mg/m2/week X 4), and prednisone (40 mg/m2/day x 28). All of the patients had been treated with the same combination during the first induction treatment. Of 266 patients (221 children and 45 adults) treated in first relapse, 141 (53%) achieved complete remission (CR; 55% of the children and 44% of the adults). Of 61 patients who were re-treated with the same combination after the second relapse, 14 (23%) achieved CR. The difference between second and third CR was statistically significant (P less than 0.0005). The median durations of second and third CR were 8 and 6 weeks, respectively. No significant difference was observed when the duration of CR was compared with the initial wbc count, age at diagnosis, or duration of first CR.

Adolescent↗

Neuropsychological study in patients with ALL. Two different CNS prevention therapies--cranial irradiation plus IT methotrexate vs. IT methotrexate alone.

Neurological, psychopedagogic, and psychologic long-term sequelae were evaluated in two groups of ALL patients in continuous CR for more than 2 years treated with two different CNS prophylaxis schemes. Group A, 19 patients (protocol 10-LLA-72 GATLA) received cranial irradiation 2400 rads plus IT MTX-DMT, and group B, 23 patients (protocol 1-LLA-76-GATLA) IT MTX-DMT only during induction and maintenance. All the patients were evaluated by performing neurological examination, EEG, EMG with nerve conduction velocity, CT scans, CSF studies, psychometric and psychologic studies, and neuropsychological evaluation. The most important findings were: 11 patients from group A (58%) showed abnormal CT (low density areas in the periventricular white matter, widening of subarachnoid space, ventricular dilatation, intracerebral calcification) and only one patient from group B showed CT abnormalities (p less than 0.0005). The neuropsychologic evaluation (performed by L. Bender technique and Picq-Vayer scale) showed more severe impairment (grade 3-4) in eight patients from group A (42%) and none in group B (p less than 0.001). Higher incidence of abnormalities in group A suggests the existence of more severe sequelae in the patients treated with cranial irradiation plus IT MTX-DMT than with IT MTX-DMT alone.

Adolescent↗

Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia.

In acute lymphoblastic leukemia (ALL), central nervous system (CNS) prophylaxis with cranial irradiation plus 5 doses of intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity started to be recognized as CT scan abnormalities and neuropsychologic alterations, mainly in children. Two questions were analyzed in the present report: (1) Will further doses of i.t. methotrexate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse in patients treated early in remission with cranium irradiation plus i.t. MTX-DMT even more? (2) Is i.t. MTX-DMT given during induction and maintenance equally as effective as cranium irradiation plus i.t. MTX-DMT? A randomized study was designed to answer the first question. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count less than 50,000 was 11% (15 of 135 patients) and was 11% (17 of 150) in the untreated group. In patients with a WBC count greater than 50,000, it was 16% (6/37) in the treated group and 19% (6/31) in the control group. No difference was observed according to treatment in both prognostic groups. Patients in this study were retrospectively compared with a consecutive protocol in which patients received 3 doses of i.t. MTX-DMT alone during induction plus 3 doses weekly during the first month of remission and every 3 mo thereafter. The incidence of primary CNS leukemia at 60 mo in patients with a WBC count less than 50,000 was 20% in the irradiated group and 32% in the group with i.t. MTX-DMT alone. This difference was not significant. However, the relapse-free survival at 60 mo was 26% and 41%, respectively, (p less than 0.0005). The incidence of primary CNS relapse in patients with a WBC count more than 50,000 at 48 mo was 28% in the irradiated group and 42% in the nonirradiated group. The difference was not significant. The duration of complete remission was similar, remaining at 15% and 16% of patients disease-free at 48 mo, respectively. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) the use of i.t. MTX-DMT alone compares similarly with cranial irradiation plus i.t. MTX-DMT in the incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count less than 50,000 were significantly longer in those without cranial irradiation.

Adult↗

Chemoimmunotherapy with levamisole in acute lymphoblastic leukemia.

Patients with acute lymphoblastic leukemia (ALL) who were in two consecutive protocols and in complete remission (CR) with maintenance therapy, were randomized to receive or not receive levamisole. A total of 15 of 55 low-risk patients of protocol 10-LLA-72 with levamisole had relapses, compared with 25 of 54 not receiving levamisole; 67 and 49%, respectively, remain in CR at 48 months (P less than 0.025). In protocol 1-LLA-76, 14 of 91 low-risk patients on levamisole and 25 of 93 patients receiving levamisole had relapses; 78 and 61%, respectively, remain in CR at 36 months (P less than 0.05). Seventeen of 39 high-risk patients (children with a leukocyte count higher than 50,000 and adults) receiving levamisole had relapses compared with 37 of 61 not on levamisole. The DNCB skin test showed at 18 and 24 months a 74 and 85% positivity in the levamisole groups vs. a 38 and 35% positivity in the control group (P less than 0.025). We conclude that levamisole prolongs the duration of CR and survival in low-risk patients with ALL.

Adolescent↗