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E Gehan

Publications and source records attributed to E Gehan.

At least 19 recordsLinked to original sources
PubMed2002

Sample size and power determination for clustered repeated measurements.

It is common in epidemiological and clinical studies that each subject has repeated measurements on a single common variable, while the subjects are also 'clustered'. To compute sample size or power of a test, we have to consider two types of correlation: correlation among repeated measurements within the same subject, and correlation among subjects in the same cluster. We develop, based on generalized estimating equations, procedures for computing sample size and power with clustered repeated measurements. Explicit formulae are derived for comparing two means, two slopes and two proportions, under several simple correlation structures.

Alveolar Bone Loss↗
PubMed2001

Phase I and pharmacokinetic study of two sequences of gemcitabine and docetaxel administered weekly to patients with advanced cancer.

PURPOSE: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and effect of drug sequence on toxicities and pharmacokinetics of the combination of gemcitabine and docetaxel. METHODS: A total of 34 patients with advanced cancers were treated with gemcitabine and docetaxel on days 1 and 8 of each 21-day cycle according to the following dose escalation schedule: level 1, 800 and 30 mg/m2, respectively; level 2, 800 and 40 mg/m2; level 3, 1,000 and 40 mg/m2; and level 4, 1,250 and 40 mg/m2. At each dose level, at least three patients were assigned to one of the two sequences of drug administration: gemcitabine-->docetaxel or docetaxel-->gemcitabine. Once the MTD had been reached, six additional patients, who had received no more than one chemotherapy regimen, were enrolled to dose levels 3 and 4 (gemcitabine-->docetaxel) to determine the MTD in minimally pretreated patients. RESULTS: Neutropenia was the most frequent DLT with an overall incidence of 23.5%. Grade 3/4 neutropenia occurred in 62% of patients (8/13) who had received two or more prior chemotherapy regimens, but not at all (0/15) in patients who had received no more than one prior chemotherapy regimens (P< 0.001). Additional DLTs included grade 4 diarrhea and grade 4 stomatitis in one patient each. The MTD was determined to be gemcitabine 800 mg/m2 and docetaxel 40 mg/m2 in patients who had received two or more prior chemotherapy regimens. However, minimally pretreated patients (no more than one prior chemotherapy regimen) were able to tolerate higher doses with an MTD of gemcitabine 1,250 mg/m2 and docetaxel 40 mg/m2. There were no significant differences in toxicities or pharmacokinetics between the two sequences of administration. Partial and minor responses were observed in 23.5% of patients: non-small-cell lung (two of eight), gastric (two of three), head and neck (one of two), bladder (two of four) and hepatocellular cancer (one of one). CONCLUSIONS: The combination of gemcitabine and docetaxel administered on days 1 and 8 every 21 days was feasible and well tolerated in patients with advanced malignancies. The sequence of administration had no significant effect on the toxicity or pharmacokinetics of either drug. Minimally pretreated patients tolerated higher doses of this combination without significant toxicities. This schedule and combination demonstrated activity in a variety of solid tumors, and merits further evaluation.

Adult↗
PubMed2001

Ex vivo cytokine activation of peripheral blood stem cells: a potential role for adoptive cellular immunotherapy.

Ex vivo activation of peripheral blood stem cells (PBSC) using interleukin-2 (IL-2) results in cytotoxic effector cells that may possess beneficial in vivo effects. We proposed to evaluate ex vivo stimulation of PBSC using various cytokines alone or in combination to optimize their function. Cytokine-activated PBSC were analyzed for tumor-directed cytotoxicity and their ability to remove tumor cells from long-term clonogenic assays. Mononuclear cells were obtained from the apheresis products of normal donors and cultured with IL-2 (1000 U/ml), interferon-alpha (IFN-alpha) (1000 U/ml), or IL-12 (50 U/ml) either alone or in combinations at 37 degrees C and 5% CO(2) for 24 h. Colony-forming unit-tumor (CFUT) assays were initiated using cytokine-activated PBSC with varying concentrations of MCF-7 or SKBR-3 human breast cancer cells. Standard 4-h (51)Cr-release assays were performed with cytokine-activated PBSC using MCF-7 or SKBR-3 cells as targets. Activation of PBSC with IL-2, IFN-alpha, or IL-12 resulted in enhanced cytotoxicity against the two breast cancer cell lines when compared to controls. PBSC activated with IL-2 and IFN-alpha or IL-2 and IL-12 were more cytotoxic than PBSC activated with single cytokines (p = 0.0004 for MCF-7 cells and p < 0.001 for SKBR-3 cells). Using clonogenic assays, IL-2-activated PBSC reduced the number of CFU-T to a greater extent than did IL-12 or IFN-alpha-activated PBSC (p = 0.0006). However, PBSC activated with a combination of IL-2 and IFN-alpha or IL-2 and IL-12 demonstrated 95% and 90% reductions, respectively, compared to 79% reduction using IL-2-activated PBSC (p < 0.0001). The greatest reduction in cytotoxicity occurred in the cell populations depleted of CD56(+) cells (p = 0.016) and CD8(+) CD56(+) cells (p = 0.002), suggesting that the effector cell population includes a combination of cytotoxic CD8(+) T cells and CD56(+) natural killer cells. These results demonstrate that the ex vivo activation of PBSC with cytokines, either alone or in combination, enhances cytotoxicity against, and removal of two human breast cancer cells. The combinations of IL-2 with IFN-alpha or IL-12 are most beneficial in cytotoxicity and purging assays. These results could play an important role in designing adoptive cellular immunotherapy clinical trials in the autologous hematopoietic stem cell transplant setting.

Blood Component Removal↗
PubMed2000

Phase I study in advanced cancer patients of a diversified prime-and-boost vaccination protocol using recombinant vaccinia virus and recombinant nonreplicating avipox virus to elicit anti-carcinoembryonic antigen immune responses.

PURPOSE: This trial sought to determine, for the first time, the validity in human vaccinations of using two different recombinant vaccines in diversified prime-and-boost regimens to enhance T-cell responses to a tumor antigen. PATIENTS AND METHODS: Eighteen patients with advanced tumors expressing carcinoembryonic antigen (CEA) were randomized to receive either recombinant vaccinia (rV)-CEA followed by three avipox-CEA vaccinations, or avipox-CEA (three times) followed by one rV-CEA vaccination. Subsequent vaccinations in both cohorts were with avipox-CEA. Immunologic monitoring was performed using a CEA peptide and the enzyme-linked immunospot assay for interferon gamma production. RESULTS: rV-CEA followed by avipox-CEA was superior to the reverse order in the generation of CEA-specific T-cell responses. Further increases in CEA-specific T-cell precursors were seen when local granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose interleukin (IL)-2 were given with subsequent vaccinations. The treatment was extremely well tolerated. Limited clinical activity was seen using vaccines alone in this patient population. Antibody production against CEA was also observed in some of the treated patients. CONCLUSION: rV-CEA was more effective in its role as a primer of the immune system; avipox-CEA could be given up to eight times with continued increases in CEA T-cell precursors. Future trials should use rV-CEA first followed by avipox-CEA. Vaccines specific to CEA are able to generate CEA-specific T-cell responses in patients without significant toxicity. T-cell responses using vaccines alone may be inadequate to generate significant anticancer objective responses in patients with advanced disease. Cytokines such as GM-CSF and IL-2 may play a key role in generating such responses.

Adult↗
PubMed2000

Hydroxychloroquine for the treatment of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. Both the disease and the medications used to treat it are associated with significant morbidity and mortality. The manifestations of chronic GVHD often resemble those of autoimmune disorders. Hydroxychloroquine (HCQ) is a 4-aminoquinoline antimalarial drug used for the treatment of autoimmune diseases. HCQ interferes with antigen processing and presentation, cytokine production, and cytotoxicity and is synergistic with cyclosporine and tacrolimus in vitro. Forty patients with steroid-resistant or steroid-dependent chronic GVHD were enrolled in a phase 2 trial of HCQ 800 mg (12 mg/kg) per day. Three complete responses and 14 partial responses were seen in 32 evaluable patients (53% response rate). All responders tolerated a >50% reduction in their steroid dose while receiving HCQ. Clinical response occurred at a median of 8 weeks (range, 4 to 24 weeks). No hematologic, hepatic, renal, or retinal toxicity was associated with HCQ. In light of its mechanisms of action, clinical activity for GVHD, and low toxicity profile, HCQ may be useful in a multiagent approach for the treatment of extensive chronic GVHD.

Adolescent↗
PubMed1999

Survival after autologous hematopoietic stem cell transplantation for patients with inflammatory breast carcinoma.

BACKGROUND: The authors retrospectively determined the clinical outcome of patients with inflammatory breast carcinoma (IBC) treated with high dose chemotherapy (HDC) and autologous bone marrow (ABM) or peripheral blood stem cell (PBSC) support. METHODS: Twenty-four consecutive patients with IBC received HDC, including escalating doses of carboplatin (range, 1.2-1.8 g/m2) and cyclophosphamide (range, 4.8-6.0 g/m2) over 3 days followed by ABM (n=5) or PBSC infusion (n=19). Restaging evaluation was performed 100 days after transplant, every 6 months for 2 years, and then yearly thereafter. After transplantation, fifteen patients received immunotherapy with interleukin-2 (IL-2) or IL-2 and interferon-alpha. RESULTS: The 2-year estimated disease free survival (DFS) and overall survival (OS) for these patients were 71% (90% confidence interval [CI], 55-87%) and 73% (90% CI, 53-93%), respectively. The median follow-up of surviving patients was 19 months (range, 8-68 months). Six patients developed disease recurrence at a median of 10 months (range, 4-16 months) after transplantation. Four of these 6 patients died from metastatic disease at a median of 18 months (range, 14-21 months). Using the generalized Wilcoxon test and the Cox proportional hazards regression model, patients with tumors that demonstrated estrogen receptors had an improved DFS (P=0.03). CONCLUSIONS: Combining HDC and ABM or PBSC for patients with IBC may yield an improved OS and DFS.

Adenocarcinoma↗
PubMed1997

Preservation of the bladder in patients with rhabdomyosarcoma.

PURPOSE: To review the pathologic findings from children with gross residual rhabdomyosarcoma (RMS) of the bladder and compare the treatment outcome of those who underwent cystectomy with those who did not. PATIENTS AND METHODS: Primary and follow-up records and pathology specimens for 28 patients with gross residual disease entered onto the intergroup Rhabdomyosarcoma Study (IRS) III were reviewed. These patients were assigned to receive 20 weeks of multiagent induction chemotherapy and 4 weeks of radiotherapy. Future therapy decisions were based on clinical and histologic evaluation at 20 weeks. RESULTS: All patients had a clinical and histologic response. Thirteen patients underwent cystectomy at intervals that ranged from 1.5 to 38 months after the start of therapy. All but one patient are alive and well without recurrence. Reasons for cystectomy included presumed evidence of tumor growth from imaging studies, findings at cystoscopy, or histologic interpretation of biopsies. In 12 of 14 specimens from 15 patients who retained their bladder, no tumor cells were seen at first or second evaluation. In cystectomy specimens, tumor cellularity was markedly reduced and all tumor cells were in varying degrees of cellular maturation. Review of primary tumor specimens showed a greater degree of cellular maturation in patients with retained bladders than in those who underwent cystectomy. CONCLUSION: Bladder RMS is responsive to chemotherapy and radiotherapy. Twelve of 26 patients showed complete loss of tumor cells after induction therapy. Cystectomy specimens showed diminished tumor cells with varying degrees of cellular maturation. It is hypothesized that these tumors may have shown further maturation and ultimate loss of matured cells with continuing therapy.

Child↗
PubMed1996

Parameningeal rhabdomyosarcoma: results of an international workshop.

PURPOSE: A retrospective analysis was performed on children with nonmetastatic rhabdomyosarcomas (RMS) involving a parameningeal site treated by one of the four major cooperative groups: Intergroup Rhabdomyosarcoma Study (IRS), International Society of Pediatric Oncology (SIOP), German Cooperative Group (CWS), and Italian Cooperative Group (ICS) to analyse survival and prognostic factors. METHODS AND MATERIALS: Between 1979 and 1989, 230 children (median age 6 years) were treated in the IRS III, SIOP 84, CWS 81, and ICS 79 studies. All patients received chemotherapy, and 203 were irradiated. Radiotherapy doses were similar in the four studies, although treatment volumes were not similar. The SIOP patients had smaller volumes treated. In addition, the SIOP patients with a low risk of meningeal involvement and children under 5 years of age were not irradiated if they had a complete response (CR) to chemotherapy. Time to initiation of irradiation was earlier in the IRS and Italian studies. RESULTS: Median follow-up was 62 months (range 22-140). The 5-year survival and 5-year event-free survival were better for the IRS study (74% and 71%) than for the other study groups (55% and 36% for SIOP, 47% and 47% for CWS, and 39% and 39% for ICS). The low-risk (LR) patients in the IRS study had improved survival. However, patients with high risk of meningeal involvement had similar survival in all four studies. The most significant prognostic factor was the size of tumor (> 5 cm). CONCLUSION: The improved results from the IRS group, especially among the LR patients, could be related to the IRS treatment employed, particularly the systematic use of radiation, to the inclusion of patients with smaller tumors, and to the routine use of quality control of radiation.

Adolescent↗
PubMed1995

Cyclophosphamide dose escalation in combination with vincristine and actinomycin-D (VAC) in gross residual sarcoma. A pilot study without hematopoietic growth factor support evaluating toxicity and response.

PURPOSE: The Intergroup Rhabdomyosarcoma Study (IRS) initiated an escalating-dose cyclophosphamide (Cyc) pilot without hematopoietic growth factor (HGF) support in combination with vincristine (Vcr) and actinomycin-D (Amd), known as VAC, to establish a Cyc dose with myelotoxicity comparable to an ifosfamide (Ifos), Vcr, and Amd combination regimen (VAI). A Cyc dose equivalent to Ifos was to be determined when comparable myelotoxicity was achieved. PATIENTS AND METHODS: Patients with either rhabdomyosarcoma or undifferentiated soft-tissue sarcoma and gross residual (clinical group III) disease were eligible for the VAC pilot. Feasibility and toxicity were evaluated in the VAC pilot at each Cyc level before escalating the dose. Starting at CYC 1.2 g/m2 dose escalation was planned at increments of 20-25% in cohorts of 8-10 patients until myelotoxicity at a severe or worse grade was seen in > 90% of the patients. RESULTS: One hundred nineteen eligible patients were evaluated for toxicity and response at four Cyc levels: 1.2, 1.5, 1.8, and 2.2 g/m2. Eight of 87 (9%) evaluable at 2.2 g/m2 had a toxic death. Six of these were attributable to myelotoxicity. Patients age 1-3 years were most vulnerable. The overall complete response (CR) rate of 68% was poorly predicted by the weeks 8 and 20 CR rates of 20 and 40%, respectively. During the first year and overall, myelotoxicity at 2.2 g/m2'1 with VAC was comparable to Ifos 1.8 g/m2'5. Cyc was relatively more myelotoxic than Ifos in the second year of the VAC pilot. Based on actual amount of drug given, a standardized Ifos dose of 9.0 g/m2 was equivalent to 2.1 g/m2 of Cyc, giving an Ifos/Cyc ratio of 4.3. CONCLUSION: Myelotoxicity using 2.2 g Cyc/m2 in a single intravenous infusion was dose limiting in this VAC pilot without HGF. In the first year and overall, myelotoxicity is comparable to that with VAI using Ifos at 9.0 g/m2. An ongoing IRS-IV randomized trial of VAC and VAI should provide a comparison of the efficacy of Ifos and Cyc in children and adolescents with embryonal or alveolar rhabdomyosarcoma and undifferentiated soft-tissue sarcomas.

Adolescent↗
PubMed1994

Retroperitoneal node biopsy in paratesticular rhabdomyosarcoma.

UNLABELLED: Retroperitoneal lymph node dissection (RPLND) was used in 121 Intergroup Rhabdomyosarcoma Study (IRS) III patients with nonmetastatic paratesticular (PT) rhabdomyosarcoma (RMS) to assess retroperitoneal lymph node (RPLN) involvement so as to determine the need for x-ray therapy (XRT). Clinical node evaluation (CNE) was accomplished by a computed tomography (CT) scan in 105 and a sonogram in six. Pathological node evaluation (PNE) was performed in 113: lymphadenectomy (9 bilateral, 85 unilateral) and biopsy in 19. Vincristine and actinomycin D were used for 1 year postoperatively in 89%; all patients who had positive PNE received RPLN XRT. This study compares CNE with PNE and evaluates predictors of relapse and survival. FINDINGS: There were clinically negative nodes (cN0) in 81% of the 121 patients. Among cN0 patients, 14% had positive nodes (pN1). Of the clinically positive (cN1) patients, 94% had pN1. RPLN relapse occurred in only two of the 121 patients. Initially both had cN0 and one had PNE that was negative. For all 121 patients, the 5-year survival was 91%. For cN0 patients, the 5-year survival was 96% compared with 69% for cN1 patients (P < .001). Among the children in whom treatment failed, nodes were cN1 in 5 of 11 (45%) compared with 15 of 107 (14%) in those whose treatment did not fail (P < .008). CONCLUSIONS: (1) Results of RPLN imaging studies were negative in 81% of patients with PT RMS (specificity 99%, sensitivity 57%). (2) RPLN recurrence is uncommon (even when RPLN are initially involved) if regional XRT and appropriate chemotherapy are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Report of the Cancer Therapy Evaluation Program monitoring plan for secondary acute myeloid leukemia following treatment with epipodophyllotoxins.

BACKGROUND: Recent reports have documented the occurrence of treatment-related acute myeloid leukemia (AML) following therapy with epipodophyllotoxins. These reports have led to growing concern among oncologists, which could lead to premature abandonment of these agents at a time when the relationship between cumulative dose of epipodophyllotoxin and risk of treatment-related AML has not been determined. PURPOSE: Because of the increasingly important role of epipodophyllotoxins in the treatment of several types of adult and pediatric tumors, the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan to obtain reliable estimates of the risk of treatment-related AML following epipodophyllotoxin treatment. METHODS: We identified 12 NCI-supported Cooperative Group clinical trials in which patients with solid tumors are being treated with epipodophyllotoxins at different cumulative doses. One trial is using a moderate dose of teniposide (900 mg/m2), and 11 trials are using etoposide at a low dose (< 1500 mg/m2), a moderate dose (1500-3999 mg/m2), or a high dose (> or = 4000 mg/m2). Cases of treatment-related AML and treatment-related myelodysplastic syndrome (MDS) (hereafter referred to as treatment-related AML/MDS) occurring in these trials are reported to CTEP, with initial analysis for each cumulative dose group triggered by the reporting of four cases of treatment-related AML/MDS in that group. For each analysis, total patient follow-up for the group is determined and cumulative 6-year incidence rate is calculated. RESULTS: Three cases of treatment-related AML and one case of treatment-related MDS (with documented monosomy 7) were reported in a group of 207 patients who received etoposide at a low cumulative dose. The calculated 6-year rate of development of treatment-related AML/MDS was 3.2% (95% upper confidence interval bounded by 7.2%). CONCLUSIONS: The 6-year cumulative rate of treatment-related AML/MDS (3.2%) is within the range previously reported for alkylator-based regimens that did not include epipodophyllotoxins. IMPLICATIONS: Previous reports have suggested that higher cumulative doses of alkylators are associated with increased risk of treatment-related AML, and a critical goal of the monitoring plan is to determine whether a similar relationship exists for the epipodophyllotoxins. Estimates will be developed for leukemogenic risk for the moderate- and high-cumulative-dose groups when four cases of treatment-related AML/MDS have been identified within each group.

Acute Disease↗
PubMed1992

Late effects of therapy in patients with paratesticular rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Committee.

PURPOSE: We report on long-term health-related problems determined from extended follow-up of 86 children and adolescents who were treated for paratesticular rhabdomyosarcoma on the Intergroup Rhabdomyosarcoma Studies I and II (IRS I-II). PATIENTS AND METHODS: Patients were treated between 1972 and 1984, and ages at diagnosis ranged from 10 months to 19 years. The majority of these patients had initial retroperitoneal lymph node dissection (RLND) or sampling performed. RESULTS: Problems related to surgical procedures included bowel obstruction in nine patients, loss of normal ejaculatory function in eight, development of a hydrocele in five, and lymphedema of the leg in five. Sequelae related to radiotherapy were difficult to assess with the exception of three patients whose remaining testes were in the field of radiotherapy. In general, kidney and bladder function were normal in patients who received radiotherapy to the paraaortic lymph nodes and/or bladder. Four patients who had abdominal radiotherapy had chronic diarrhea. Two patients had urethral strictures and urethritis. Four patients had bone or soft tissue hypoplasia in the field of radiotherapy. Chemotherapy-related late effects were primarily hemorrhagic cystitis or gonadal dysfunction after cyclophosphamide. A third of the patients who received cyclophosphamide developed hemorrhagic cystitis, and half of these had extended periods of gross hematuria after therapy was discontinued. The testicular size was small in children whose testes were irradiated and in some who received cyclophosphamide. Tanner staging was normal in 45 patients for whom it was recorded. Elevated follicle-stimulating hormone (FSH) values or known azoospermia occurred in more than half the patients for whom data were available. CONCLUSIONS: A variety of sequelae related to therapy were determined in this patient population. These findings suggest that some aspects of therapy warrant reevaluation and that improved plans for follow-up care need to be provided.

Adolescent↗
PubMed1990

Secondary surgical procedures to evaluate primary tumor status in patients with chemotherapy-responsive stage III and IV sarcomas: a report from the Intergroup Rhabdomyosarcoma Study.

Fifty children with clinical group III (localized, but unresected) or clinical group IV (disseminated) soft tissue sarcomas were entered in a trial to determine if the addition of etoposide and cisplatin to standard chemotherapy regimens and irradiation (4,000 cGy) would be tolerated by pediatric patients. Responding patients had a secondary surgical procedure performed after approximately 20 weeks of therapy for the purpose of establishing histological response, determining its extent, and removing residual tumor tissue, when feasible. Such procedures were performed in 29 of 50 (58%) of these patients, ie, 20 of 31 (65%) of those in group III, and nine of 19 (47%) of those in group IV. Surgical procedures consisted of exploration of the site and biopsy (only) in 16 patients; grossly complete tumor excision in nine; and subtotal tumor excision in four. In nine patients (six in group III, three in group IV) apparent total excision of a previously unresected primary tumor mass was accomplished at second surgery. One distant but no local relapse has occurred in this group, and eight of nine have survived (five of six with identified tumor in the specimen) for a duration of 232 to 348 weeks (six greater than 260 wks), suggesting that among patients with primary tumors in selected sites, with either stage III or stage IV disease, excision of residual masses following intensive chemotherapy/radiotherapy regimens may favorably influence outcome. Local relapse subsequently occurred in seven of 18 patients in whom tumor tissue could not be identified in biopsy specimens or in excised masses taken from the primary site at second surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Prognosis in children with rhabdomyosarcoma: a report of the intergroup rhabdomyosarcoma studies I and II. Intergroup Rhabdomyosarcoma Committee.

Prestudy patient characteristics and specific therapy of all eligible patients with rhabdomyosarcoma entered into Intergroup Rhabdomyosarcoma (RMS) Studies I (IRS-I) (1972 to 1978, n = 686) or II (IRS-II) (1978 to 1984, n = 1,002) were examined for their relationship to survival within each of the four clinical groups using univariate and multivariate analyses. The estimated survival at 5 years from the start of treatment was 56% in IRS-I and 62% in IRS-II (P = .006). The largest survival difference between studies was in patients with group III tumors (52% v 65%). The clinical group was the most important patient characteristic related to survival in both studies. Survival progressively decreased for patients from clinical group I (localized disease, completely resected) to group IV (metastatic disease at the onset). In clinical group I, the only patient characteristic consistently related to survival was histology. Patients with alveolar tumors had the poorest survival, while those with botryoid/embryonal lesions had the best survival. In clinical group II, no characteristic was consistently related to survival. In clinical group III, an orbital primary site was associated with a favorable survival. In clinical group IV, patients with genitourinary tumors had a significant survival advantage. Use of disease-free survival as an end point gave very similar results. This information, from the largest available data base on prognostic indicators in childhood RMS in the context of aggressive multimodal therapies, is being used to plan therapy in the forthcoming study (IRS-IV).

Adolescent↗
PubMed1986

Effect of azimexon therapy on host defense parameters and disease-associated symptoms in the acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC).

Azimexon, a 2-cyan-aziridinyl immune modulator, was given at a dose of 250 mg/m2/day for 10 days IV to 12 patients with AIDS and 16 with AIDS related complex (ARC). A decrease in total number of AIDS related symptoms from 43 to 24 and in mean number from 2.6 to 1.5 was observed among ARC patients (p less than .01). The most commonly improved symptoms were diarrhea, fatigue, and weight loss with the least frequently improved being lymphadenopathy. The following improvements in immune parameters were observed among ARC patients. DTH to recall antigens improved with an increase in number of positive tests from 35 to 47 and in mean number of positive skin tests from 2.2 on day 0 to 2.9 on day 14 (P less than .05). The geometric mean of the absolute lymphocyte count was 1.395 X 10(3)/microliter on day 0 with a significant increase of 18.0 percent on day 5 (P less than .01) and a 7.7 percent increase on day 21. The geometric mean of the OKT4+ cells on day 0 was 0.250 X 10(3)/microliter with a 33.3 percent increase on day 5 (P less than .07) and a 14.1 percent increase on day 21. T4/T8 ratio increased by 32.7 percent on day 5 (P less than .05) and by 19.4 percent on day 21 from an initial geometric mean of 0.339 X 10(3)/microliter on day 0. The geometric mean of GVH responses increased by 18.2 percent on day 5 (P less than .05) and by 24.0 percent on day 21 (P less than .07) from an initial value of 41.04 mm3. No symptomatic or immunologic improvements were observed among AIDS patients, but rather a significant decrease in mitogenic responses. PHA responses decreased by 70.3 percent on day 5 (P less than .05) and 42.2 percent on day 21 from an initial geometric mean of 4.02 X 10(3) cpm/10(3). Con-A responses decreased by 75.1 percent on day 5 (P less than .05) and increased by 20.3 percent on day 21 from an initial value of 1.14 X 10(3)/10(5) cells. Pretreatment number of absolute OKT4+ cells was the most significant prognostic survival variable. Thus, 8/9 patients with less than 0.10 X 10(3) OKT4+ blood cell/microliter subsequently died as compared to only 1/17 with greater than or equal to 0.10 X 10(3) OKT4+ cells (p less than .001). The only toxic effect of this treatment was mild hemolysis which disappeared upon cessation of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS-Related Complex↗
PubMed1985

Local recurrence, rate and sites of metastases, and time to relapse as a function of treatment regimen, size of primary and surgical history in 62 patients presenting with non-metastatic Ewing's sarcoma of the pelvic bones.

This report reviews the experience of 62 patients who presented between 1972 and 1978 with non-metastatic Ewing's sarcoma of the pelvis and were entered on IESS I. Seventeen patients (27%) developed a local recurrence, 38 patients (61%) demonstrated metastases and 21 (34%) neither. In the dose range 4000 rad to 6000 rad no dose response could be detected for local control of tumor. Forty-six patients (74%) had a biopsy or exploratory surgery only, 5 patients (8%) had an incomplete resection and 11 patients (18%) had a complete resection of their tumor. In the 46 patients having a biopsy only, 13 developed a local recurrence (28%) as compared to 2 of 11 patients undergoing a complete resection (18%). The most common sites for metastases were lung in 19 patients (31%) and bone in 23 patients (37%). No significant difference was noted in the frequency of overall metastases or metastases to any site between those patients receiving one of the three treatment regimens used in IESS I: VAC and Adriamycin (regimen I), VAC alone (regimen II) and VAC plus bilateral pulmonary irradiation (regimen III). At a median follow-up of 135 weeks no significant difference in median survival could be detected in patients with pelvic primaries between regimens I, II and III. The mean diameter of the pelvic primaries was comparable to the nonpelvic, however, one half of the pelvic cases were in the range 10-15 cm. The median time to relapse of the 241 non-pelvic patients on IESS I was 222 weeks as contrasted with the median time to relapse of 92 weeks in the 62 pelvic patients on the same study (p = 0.002). The possible reasons for the poor prognosis of pelvic primary patients are discussed together with treatment policies that might improve the survival of this group of patients.

Adolescent↗