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Biomedical subjects

E Gehan

Publications and source records attributed to E Gehan.

33 records · Page 2Linked to original sources

Chronic myelogenous leukemia: a multivariate analysis of the associations of patient characteristics and therapy with survival.

The prognostic importance of patient pretreatment clinical and laboratory features was investigated in a group of 303 patients with Philadelphia chromosome-positive benign-phase chronic myelogenous leukemia. Intensive chemotherapy was given to 97 patients, and 78 underwent an early elective splenectomy. The overall median survival time, dated from hospital admission, was 39 months. Patient characteristics associated with shortened survival were age 60 years or older, black race, the presence of hepatomegaly, splenomegaly, symptoms, weight loss, and poor performance status. Adverse blood and bone marrow parameters were anemia, thrombocytosis or thrombocytopenia, a high proportion of peripheral blasts plus promyelocytes or of basophils, a high proportion of marrow blasts or basophils, decreased marrow megakaryocytes, and cytogenetic abnormalities in addition to the Philadelphia chromosome. Several of these factors were interrelated. A multivariate regression analysis demonstrated that the combination blood basophilia, race, additional cytogenetic abnormalities, age and marrow basophilia had the strongest predictive relationship to survival time. This resulted in a model segregating patients into low-, intermediate-, and high-risk groups, with median survivals of 53, 39, and 25 months, respectively. Another model was derived that did not include the marrow features and identified splenomegaly and platelet counts as adding to the prognosis prediction by blood basophilia, race, and age. Evaluation of the effect of therapy, after adjusting for differences in prognostic characteristics, showed that intensive chemotherapy was associated with survival prolongation among patients at intermediate and high risk of death. We conclude that a combination of pretreatment factors identifies different risk subcategories in patients with chronic myelogenous leukemia and is helpful in assessing overall prognosis and treatment effect.

Adult↗

Improved prospects for long-term survival in adults with acute myelogenous leukemia.

An improved complete remission rate in acute myelogenous leukemia (AML) has been noted since cytarabine and anthracyclines were introduced into clinical practice. Forty-one (9%) of 457 patients with AML treated between 1965 and 1976 have survived more than five years. The proportion of five-year survivors for patients treated between 1973 and 1976, 1970 and 1972, and 1965 and 1969 were 11.8%, 8.8%, and 1.8%, respectively. The major factor influencing five-year survival was whether or not patients were treated with cytarabine alone or combined with an anthracycline. Thirty-six (17%) of the 207 complete responders remained in continuous complete remission for more than five years. Twenty-four of the 36 patients who are in remission for more than five years have not been receiving chemotherapy for more than five years and are considered potentially cured.

Adolescent↗

Intergroup Hodgkin's disease in children study of stages I and II: a preliminary report.

The intergroup study of involved-field (IF) radiotherapy, IF radiotherapy plus MOPP chemotherapy, and extended-field (EF) radiotherapy for treatment of Hodgkin's disease in children has assessed 305 patients. Of these, 279 were "not ineligible" (no mediate cause for disqualification). Among 223 randomized patients, 144 were evaluable, 131 had documentation of complete or partial remission, 20 of the remitters relapsed, and two died. Among 62 nonrandomized patients with favorable presentations (unilateral upper neck, unilateral inguinal, or massive mediastinal disease), 29 had documented remission, two relapsed, and none died. Length of initial disease control (LIDC) was used to measure duration of response. LIDC was best in patients given IF plus MOPP, and 95% are disease free. EF was better than IF radiotherapy (P = 0.004). Of the disease characteristics prognostic for response (stage, histologic subtype, and presence of symptoms), only the last factor had a statistically significant effect on LIDC (P = 0.004). Ninety-six percent of the patients survive. Using criteria developed by the committee, 23% of the staging procedures reviewed were nonevaluable and 28% of the radiotherapy treatments were nonevaluable. The necessity for criteria for evaluation of staging and treatment is certain. Length of followup is too short for correlations of treatment with significant late effects and for relevant therapeutic recommendations.

Antineoplastic Agents↗

A four-year experience with anthracycline, cytosine arabinoside, vincristine and prednisone combination chemotherapy in 325 adults with acute leukemia.

Combination chemotherapy with an anthracycline, Adriamycin or rubidazone, cytosine arabinoside, vincristine and prednisone resulted in a complete remission rate of 62% in 325 consecutive unselected adults with acute leukemia. The results by morphologic categories were 58% for acute myelogenous leukemia (AML), 70% for acute undifferentiated leukemia (AUL), and 77% for acute lymphoblastic leukemia (ALL). The median survival was 43 weeks. Ten percent of all patients are projected to be alive and in remission at five years. The median remission duration for the whole group was 51 weeks, durations being significantly longer for AML (60 wks) than ALL (30 wks) and AUL (21 wks). Central nervous system involvement was uncommon in AML (4%), but much more common in patients with AUL (37%) and ALL (32%). One in five complete responders with AML is projected to be in their first remission at five years off all chemotherapy. Age, sex, morphology, cytogenetic pattern, temperature of presentation, and presence of a documented preceding hematologic abnormality are found to be significant variables for response and survival.

Adolescent↗

Radiation to regional nodes for rhabdomyosarcoma of the genitourinary tract in children: is it necessary? A report from the Intergroup Rhabdomyosarcoma Study No. 1 (IRS-1).

Fifty-eight children with genitourinary rhabdomyosarcoma are reported. Lesions involved the bladder (22), prostate (14), vagina/uterus (6), and paratesticular tissues (16). Fifteen of 58 had positive sampling of regional lymph nodes. Eleven of 15 received radiation to no more than 4500 rad in most cases, and 9 of 11 are diseases free. Two of 15 had no radiation and are disease free also. Twenty-three of 58 had negative nodes. Six of 23 had radiation to these nodal areas and 4 of 6 are disease free. Fifteen of 17 patients had no radiation and are disease free also. Sixteen of 20 patients with no node sampling are disease free; 9 of 16 had radiation but 7 of 16 did not. All patients in the Study had intensive systemic maintenance chemotherapy. One 1 patient failed in regional nodes despite 4500 rad to these node echelons. We suggest chemotherapy and radiotherapy, not to exceed 3500 rad in four weeks, to known residual disease including regions from which positive nodes have been obtained.

Child↗

Unmaintained remissions in multiple myeloma.

Twenty-eight patients with multiple myeloma responding to prior melphalan-prednisone combinations, but without additional chemotherapy, were followed until relapse. Patients receiving no further treatment had a median survival time similar to that of those receiving indefinite courses of melphalan-prednisone or carmustine-prednisone. Prolonged periods of unmaintained remission occurred primarily in patients without extensive disease at the time of diagnosis or in whom the abnormal protein disappeared from the electrophoresis strip. The initial relapse after an unmaintained remission was controlled in 80% of patients with the resumption of melphalan-prednisone, but second remissions were usually less marked in degree and shorter in duration. Results supported the long-term evaluation without chemotherapy of selected patients with low numbers of plasma cells after treatment who were likely to experience long durations of disease stability and respond again to retreatment with melphalan-prednisone.

Cell Transformation, Neoplastic↗

Combination therapy for multiple myeloma.

The effect of six different chemotherapy regimens were evaluated in 462 previously untreated patients with multiple myeloma. In comparison with other treatments, drug combinations that included vincristine and were given at 3-week intervals were associated with higher response rates and longer survival times. No gain was noted from the use of Adriamycin or from combinations of alkylating agents unless vincristine was given and the treatment intervals were short. Seventy-one responding patients were allocated at random to maintenance treatment with intermittent courses of either azathioprine--prednisone or a combination of melphalan--cyclophosphamide--carmustine (BCNU)--prednisone. The survival time was not prolonged with either maintenance treatment in comparison with that for responding patients continued on other therapies or on no therapy in previous studies. Attempts to reduce tumor was maximally with a change in the therapeutic modality, such as with immunotherapy or radiotherapy, remain to be evaluated.

Antineoplastic Agents↗

Late intensification therapy for acute leukemia in remission. Chemotherapy and immunotherapy.

Nineteen patients in continous complete remission of acute leukemia for at least one year received late intensification therapy, after which they received no further chemotherapy, but most received BCG immunotherapy. Five patients have relapsed. The 14 patients still in remission have been followed up for at least 60 weeks after late intensification, with a median time of 98 weeks. The length of complete remission subsequent to a comparable time was 44 weeks for a reference control group and 24 weeks for a matched control group. These results support this type of approach for long-term control of acute leukemia in adults.

Acute Disease↗

Randomized prospective trial comparing 5-fluorouracil (NSC-19893) to 5-fluorouracil and methyl-CCNU (NSC-95441) in advanced gastrointestinal cancer.

The Southwest Oncology Group has confirmed the superiority of 5-fluorouracil (5-FU) and methyl-CCNU versus 5-FU weekly as treatment for patients with advanced gastrointestinal cancers. The drug combination produced a PR rate of 29.3% compared to the single-drug arm rate of 10.6%; however, the two-drug arm produced much more toxicity. Despite the improved response rate no improvement in survival was observed.

Adenocarcinoma↗

Medical registers as historical controls: analysis of an open clinical trial of inosiplex in subacute sclerosing panencephalitis.

Clinical trials of treatments for rare or fatal diseases must often use historical rather than randomized concurrent controls. Randomized trials may not be possible if (1) the number of patients available is quite small, (2) ethical considerations discourage the assignment of patients to control treatments known to be ineffective or (3) some evidence suggests that the proposed new treatment is substantially more effective than the control. We suggest that, when randomization is not feasible, adequately maintained medical registers can serve as a source of control patients. Investigators must pay careful attention to prognostic factors that might bias the results. However, statistical techniques for controlling such bias exist and, if these are properly employed, registry-derived historical controls can be used to evaluate the effectiveness of treatment.

Clinical Trials as Topic↗

A feasibility, toxicity, and early response study of etoposide, ifosfamide, and vincristine for the treatment of children with rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study (IRS) IV pilot study.

PURPOSE: The purpose of this study was to determine the feasibility, toxicity, and early response of patients with clinical group III rhabdomyosarcoma (RMS) to a chemotherapy regimen of etoposide (ETOP), ifosfamide (IFOS), and vincristine (VCR) with hyperfractionated radiation therapy (XRT). PATIENTS AND METHODS: Sixty-eight patients aged < 21 years, previously untreated, with clinical group III RMS or undifferentiated sarcoma with normal organ function were eligible for this study. Chemotherapy was as follows: weeks 0-8: IFOS 1.8 g/m2/day X 5 days every 3 weeks X 3 (with mesna), ETOP 100 mg/m2/day X 5 days every 3 weeks X 3, and VCR 1.5 mg/m2/week X 9; weeks 9-16: hyperfractionated XRT (except patients with parameningeal tumors with meningeal extension, who received XRT on day 0), IFOS/mesna weeks 9, 12, 16, and VCR weeks 9, 10, 11, 12, 16; weeks 20-99; IFOS/mesna q 3 weeks X 2, ETOP q 3 weeks X 2, and VCR weekly X 6 weeks. Four drug cycles were repeated every 9 weeks, beginning at week 29. In January 1991, the duration of therapy was reduced to 12 courses due to emerging evidence of IFOS-induced renal tubular dysfunction. RESULTS: Of the 62 patients evaluable for response, 45 (73%) achieved a complete response. There were three fatal toxicities due to infection. Life-threatening neutropenia was seen in 55 of 60 patients, and life-threatening infections occurred in 27 of 60 patients. Twenty-five patients (42%) developed some degree of neurotoxicity from vincristine. Eleven patients (18%) developed nephrotoxicity, 7 cases of which were severe; 6 of the 11 patients who developed nephrotoxicity were < 2 years old. CONCLUSIONS: This pilot study had toxicity and response rates comparable to the other two Intergroup Rhabdomyosarcoma Study (IRS)-IV pilot trials of vincristine-actinomycin-cyclophosphamide and vincristine-actinomycin-ifosfamide and is, therefore, being evaluated in the current IRS randomized trial. Due to the high incidence of life-threatening neutropenia and infections, the use of growth factors is now routine. Five of 11 patients who developed nephrotoxicity did so after more than eight courses of IFOS; therefore, the current randomized trial limits IFOS to a total of eight courses.

Adolescent↗