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At least 1,117 records · Page 62Linked to original sources
PubMed1984

BCNU (1,3-bis-(2-chloroethyl)-1-nitrosurea) lung. Drug-induced pulmonary changes.

The occurrence of pulmonary disease associated with long-term BCNU therapy is reported in two patients treated for astrocytoma grade II whose clinical presentations of pulmonary complications and corresponding tissue alterations showed striking differences. One patient presented with a dramatic, fulminating, and rapidly fatal pulmonary disease. His lungs revealed atypical proliferation of pneumocytes, moderate interstitial inflammation, fibrosis and intra-alveolar hyalin membranes. The second patient presented with slowly progressive dyspnea, ultimately leading to death secondary to severe diffuse alveolar septal fibrosis. Individual differences in response to toxicity are suggested and discussed.

Adult↗
PubMed1984

Chemotherapy for multiple myeloma.

The effects of eight different drug combinations were evaluated in 256 patients with multiple myeloma. The response rate and time to remission were superior from regimens that added both vincristine and Adriamycin (doxorubicin) to an alkylating agent-prednisone combination. There was no improvement in response rate or survival time from two alternating drug combinations evaluated in an attempt to achieve more marked tumor reductions and to delay the emergence of resistant subclones. The addition of levamisole during remission maintenance did not improve survival time. Results supported the utility of unmaintained remission follow-up in selected patients with marked reductions in myeloma cell mass.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Combination chemotherapy plus levamisole in the treatment of disseminated malignant melanoma. A Southwest Oncology Group study.

Two hundred-eighty patients were randomized to receive either BCNU, hydroxyurea and imidazole carboxamide (BHD), BHD plus levamisole, or high-dose DTIC plus actinomycin D. There was no difference in response rate in the three groups (24%, 25% and 22%). Females responded better than males and, as expected, those with a better performance status responded more favorably than those with poor performance status. Patients whose primary site of melanoma was on the extremities did significantly better than those melanomas originating on the trunk or head and neck. Patients with lymphocyte counts greater than 2000/mm3 fared better than those with lymphopenia. Those responders who received high-dose DTIC plus actinomycin D had a significantly longer length of response than those receiving the immunotherapy limb. This was also true in those patients who had a prior disease-free interval of greater than 6 months before being placed in this study. Although there was no difference in survival from the start of treatment in all patients, those patients receiving high-dose DTIC plus actinomycin D and who had a prior disease-free interval of greater than 6 months, had significantly superior survival when compared to the immunotherapy limb. It is concluded that the addition of Levamisole to BHD does not improve response rate and may in certain subsets be detrimental to disease-free response and survival. High-dose DTIC plus actinomycin D is equally effective to BHD.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Dimethyl triazeno imidazole carboxamide and combination therapy for melanoma. IV. Late results after complete response to chemotherapy (Central Oncology Group protocols 7130, 7131, and 7131A).

The results of three Phase III studies of DTIC in 580 patients with metastatic melanoma were reviewed to evaluate the subsequent course of 26 patients who achieved a complete response (CR) to chemotherapy. The majority (17 of 26) of these patients had soft tissue metastases. Six of the 26 patients remained in CR at last report (30-259 weeks), two died of other causes while remaining free of melanoma, and 18 relapsed and died. Ninety-five percent of the 26 patients were alive at 1 year, and survival was 31.1% at 72 months. Seven of the eight patients with sustained remission received chemotherapy for at least 6 months after CR developed, whereas 10 of 18 relapsing patients were treated for less than 6 months after CR was achieved. Long-term sustained CR to chemotherapy occurs in 1% to 2% of patients treated with DTIC, and late relapse is rare in patients who remain in CR for 2 years.

Adult↗
PubMed1984

Successful pregnancy following continuous treatment with combination chemotherapy before conception and throughout pregnancy.

A 21-year-old woman with diffuse histiocytic lymphoma received combination chemotherapy continuously for 16 months before conception and throughout pregnancy. Procarbazine and BCNU were given for 5 months before conception and throughout the first and second trimesters, and streptozotocin was given throughout the third trimester. A male infant who was phenotypically and genotypically normal was delivered. The authors reviewed the literature regarding chemotherapeutic agents given during the first trimester of pregnancy. Although most chemotherapeutic agents are teratogenic in the animal model, the incidence of teratogenicity of chemotherapeutic agents given to humans in the first trimester of pregnancy is 12.7%. This represents a fivefold increase in teratogenicity. As yet the administration of chemotherapeutic agents in the second and third trimesters has not resulted in teratogenicity. This information may help the physician when deciding whether to treat pregnant patients with chemotherapeutic agents during the first trimester or whether to continue treatment when the patient has become pregnant while receiving these agents.

Abnormalities, Drug-Induced↗
PubMed1985

Combined modality therapy for mediastinal Hodgkin's disease. Prognostic significance of constitutional symptoms and size of disease.

Combined modality therapy was used in an attempt to increase the complete remission rate and survival of previously untreated patients with Hodgkin's disease. MOPP (nitrogen mustard, vincristine, procabazine, prednisone) chemotherapy was followed by radiotherapy. The median duration of follow-up exceeded 5 years. Complete remissions were achieved in 63 of 71 patients (89%) with mediastinal masses. The actuarial survival of 10 years was 72% for patients with small mediastinal masses (mediastinal mass ratio less than 0.35) and 46% for patients with large mediastinal masses (P less than 0.05). The corresponding disease-free survival figures were 69% and 46%, respectively (P less than 0.05). A small mediastinal mass did not affect prognosis. Systemic symptoms especially affected the prognosis in patients with a large mediastinal mass, since in symptomatic patients the actuarial survival and freedom from relapse were 19%, whereas all asymptomatic patients survived without relapse. In patients with a small mediastinal mass, systemic symptoms had no significant effect on the actuarial survival or disease free survival. Age and stage did not affect the prognosis in patients with large mediastinal masses. It was concluded that MOPP chemotherapy followed by radiotherapy was an adequate treatment for asymptomatic patients with large mediastinal disease. However, in symptomatic patients with large mediastinal masses, this treatment was clearly inadequate.

Adolescent↗
PubMed1985

Pediatric Oncology Group experience with modified LSA2-L2 therapy in 107 children with non-Hodgkin's lymphoma (Burkitt's lymphoma excluded).

From September 1976 to August 1979 the Pediatric Oncology Group accessed 145 children to study the effectiveness of modified LSA2-L2 therapy for the treatment of non-Hodgkin's lymphoma (NHL). Burkitt's lymphoma patients were ineligible; E-rosette-positive patients with greater than or equal to 25% blasts in the marrow entered after February 1977 were reported separately. Radiotherapy could be used to treat patients with compressive mediastinal disease at diagnosis and was prescribed for those with residual abdominal disease as demonstrated by second-look surgery on completion of induction chemotherapy. Confirmation of diagnosis by the Pathology Panel and Repository Center for Lymphoma Clinical Trials was mandatory. Diagnostic tissues of 131 patients were reviewed. Among 107 evaluable patients, 91 (85%) achieved complete remission. Differences in response rates among the three major histologic groups (lymphoblastic, undifferentiated, and large cell) were of statistical significance, with response being poorest for diffuse undifferentiated lymphoma (P = 0.03). Failure-free survival did not differ significantly for the three major histologic diagnoses. While response rate was lowest for Murphy Stage III patients (79%), the differences among the stages were not significant. Stage was not a significant prognostic factor for failure-free survival (P = 0.08). The number of patients still at risk and the Kaplan-Meier estimate of percentage of patients remaining at risk after 3 years is: Stage I, 8 (100%); Stage II, 10 (67%); Stage III, 28 (57%); Stage IV, 6 (39%); and greater than 25% blasts, 1 (13%). Stage III failure curves for lymphoblastic disease show continuing stepwise failure through 3 years. Among patients with diffuse large cell and undifferentiated disease, most failures occurred by 8 months. M1 and M2 levels of marrow involvement were not prognostic among children with lymphoblastic disease. The presence of a mediastinal mass was a significant factor contributing to failure in children with lymphoblastic disease without marrow involvement. Leucocytosis greater than 10,000/1, was a significant (P = less than 0.001) factor predicting failure-free survival for patients with large cell lymphoma. The delivery of radiotherapy was not a significant factor in achieving remission. No consistent benefit resulted from using radiotherapy to treat postinduction residual disease demonstrated on second-look exploration. The LSA2-L2 regimen was associated with considerable toxicity, severe or worse in 77% and life-threatening to 40% of these patients. Four died of toxicity. However, therapy was given more easily and safely as investigator experience increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

Phase I trial of thermochemotherapy for brain malignancy.

High-grade primary and refractory brain tumors and metastases to the brain from other primary sites are associated with a grave prognosis. Treatment, usually palliative, consists of some combination of surgery, radiation, and chemotherapy. Recently, noninvasive hyperthermia by magnetic-loop induction has been safely used to treat patients with advanced cancer in extracranial sites. Both disease regression and disease stabilization have been observed. This technique was recently applied to brain tumors in an animal model, and its safety was again demonstrated. As a result, a Phase I trial of noninvasive localized hyperthermia in combination with intravenous chemotherapy has been carried out in ten patients whose primary or metastatic brain tumors failed to respond to standard therapy. Ten patients underwent 23 thermochemotherapy sessions using the magnetic-loop induction device. The median, maximum temperature of normal brain after 1 hour of hyperthermia was 41.1 degrees C (range, 38.6 degrees C-43.4 degrees C); the median, maximum temperature of brain tumor was 42.5 degrees C (range, 38.8 degrees C-46.3 degrees C) (P less than 0.01). The temperatures of both the normal brain and brain tumor were obtained during 18 treatments. The tumor temperature was greater than the normal brain temperature in 15 of 18 treatments. In 78% of the treatments, the measured tumor temperature reached at least 42 degrees C, whereas the normal brain reached 42 degrees C in only 13% of the treatments. These data demonstrate the "selective inability" of brain tumor tissue to dissipate heat. Vital signs, intracranial pressure, and neurologic status were monitored throughout the hyperthermia treatments. No mortality or increase in chemotherapeutic toxicity could be attributed to the thermochemotherapy. In addition, there were no local complications or permanent neurologic complications. Two patients with elevated intracranial pressure before therapy had transient neurologic deficits that may have been exacerbated by the hyperthermia. It is concluded that this new, noninvasive modality not only produced effective intracranial tumor heating, but could be performed safely with the proper precautions. Phase II trials are warranted.

Adult↗
PubMed1986

Intracarotid BCNU leukoencephalopathy.

Intracarotid 1,3-bis(2-chloroethyl)-1-nitrosurea (BCNU) is now a frequently used chemotherapeutic agent for high-grade glial neoplasms. The toxicity from such therapy has not been well-documented. A 50-year-old man with a left frontoparietal grade 4 astrocytoma received three injections of intracarotid BCNU, 400 mg each, over a 2-month period. No radiation or other chemotherapy was ever given. He tolerated the BCNU injections well, with some reduction of tumor bulk, until the third dose. After his last injection, his condition gradually deteriorated; he became obtunded, and died 5 weeks later. At autopsy, the brain showed extensive cavitation and coagulative necrosis, fibrinoid vascular necrosis, edema, swollen axons, and bizarre cellular morphologic features confined to the BCNU perfusion territory. Grade 4 astrocytoma remained in the right hemisphere and in the left occipital lobe, sites outside the area of BCNU perfusion. Intracarotid BCNU can result in a severe leukoencephalopathy similar to that seen with methotrexate or delayed radionecrosis.

Astrocytoma↗
PubMed1986

Alternating sequential combination chemotherapy in the management of advanced Hodgkin's disease. A Southeastern Cancer Study Group trial.

The Southeastern Cancer Study Group has explored the use of alternating sequential combination chemotherapy in advanced Hodgkin's disease. Two hundred twelve evaluable patients were randomly assigned to treatment with the six-drug combination, BCNU, cyclophosphamide, vinblastine, procarbazine, prednisone, and bleomycin (BCVPP-Bleo) or with the same drugs alternating in monthly cycles with doxorubicin, dacarbazine, and bleomycin. Both regimens produced complete response rates of approximately 73%. The duration of remission and survival were similar for the two treatment regimens. Although our sequence of combinations does not rigorously meet the criteria for "non-cross-resistant" our results do not lend support to the hypothesis that alternating sequential non-cross-resistant drug combinations improves the outcome in advanced Hodgkin's disease.

Adult↗
PubMed1987

High dose cyclophosphamide, BCNU, and VP-16 (CBV) as a conditioning regimen for allogeneic bone marrow transplantation for patients with acute leukemia.

A high dose combination chemotherapy regimen (CBV) consisting of cyclophosphamide (1.5 gm/m2 day 1 to day 4); BCNU (300 mg/m2 day 1) and etoposide (100 mg/m2 every 12 hours for 6 doses), followed by bone marrow transplant from human leukocyte antigen (HLA) identical sibling donors, was evaluated in 29 patients in whom acute leukemia was in relapse or remission. Engraftment of donor cell type occurred in all but one of 21 patients, in whom marker differences between donor and recipient were established. Two of 11 patients transplanted during relapse of the disease, lived beyond 1 year after bone marrow transplantation. One patient died free of leukemia, 41 months after transplantation of meningitis. Two of seven patients transplanted during the second remission of the disease, are alive and free of leukemia at 42+, and 8+ months. All patients transplanted during the third or fourth remission of the disease have died from either a further relapse, or transplant related causes. The low incidence of organ toxicity with CBV allows for further dose escalation of its drug components.

Acute Disease↗
PubMed1987

The effect of intensive intermittent maintenance therapy in advanced low-grade non-Hodgkin's lymphoma.

One hundred and eleven patients with low-grade histology non-Hodgkin's lymphoma achieving a restaged complete response to one of three induction therapies on Eastern Cooperative Oncology Group (ECOG) protocol EST 2474 were randomized to receive either maintenance treatment with BCNU, cyclophosphamide, vincristine, and prednisone (BCVP) given every 6 weeks for an additional 18 months or no further therapy. Overall toxicity was moderate. The median progression-free survival (PFS) on maintenance therapy was 3.2 years versus 2.0 years for those observed without treatment (P = 0.02). Progression-free survival was significantly shorter for patients with nodular and diffuse pattern (ND), histiocytic or mixed histology compared with pure nodular lymphocytic, or poorly differentiated counterpart (P = 0.0007), thus confirming the prognostic significance of histologic subtypes. However, the overall survival of patients was not improved by maintenance treatment, suggesting that therapy upon relapse was an equally effective alternative clinical strategy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Medulloblastoma at the joint center for radiation therapy between 1968 and 1984. The influence of radiation dose on the patterns of failure and survival.

In order to assess the efficacy of high-dose irradiation to the posterior fossa and low-dose irradiation to the spinal axis, we reviewed the results of 60 patients with biopsy-proven medulloblastoma treated at the Joint Center for Radiation Therapy (JCRT) between 1968 and 1984. The 5- and 10-year actuarial survival rates for all patients were 68% and 44%, respectively. The median time to recurrence was 19 months. Extent of surgery, age, and radiation dose to the posterior fossa all were of prognostic value. Complete or subtotal gross resection appeared to be a favorable prognostic indicator compared with biopsy only (P less than 0.05), with a 69% versus 40% actuarial survival rate at 5 years, respectively. Infants 2 years of age or less had a diminished 5-year actuarial survival rate of 48% (P less than 0.05) compared with older age groups. The posterior fossa was the predominant site of recurrence and accounted for 78% of all failures. Local control in the posterior fossa was dose dependent. Seventy-nine percent of the tumors that received 5000 cGy or greater were controlled versus only 33% of the tumors that received less than 5000 cGy (P less than 0.02). There were no supratentorial failures, and there was only one isolated spinal cord failure. There were no solitary spinal failures in 24 patients who received a median dose of only 2400 cGy to the spinal axis. We concluded that low-dose irradiation to the spine and whole brain may be indicated with maintenance of a posterior fossa dose of greater than 5000 cGy.

Adolescent↗
PubMed1988

Factors of prognostic importance in childhood non-Hodgkin's lymphoma treated with two modified LSA2-L2 protocols. A multivariate analysis approach.

The results of therapy given to 74 children with advanced disease, abdominal non-Hodgkin's lymphoma were retrospectively evaluated with respect to the major prognostic factors related to disease outcome. The first 36 patients admitted in the study were treated with a modified LSA2-L2 protocol, and the remaining patients received the same regimen with the addition of intermediate-dose methotrexate (MTX) intravenously during the induction phase (LSA2-L2-MTX). The last ten patients admitted were given a leucovorin rescue along with the administration of MTX. The relative efficacy of the LSA2-L2-MTX over the baseline LSA2-L2 regimen was analyzed by multivariate statistical methods taking into consideration several candidate coprognostic factors. The risk of treatment failure was substantially reduced (55%) with the use of the LSA2-L2-MTX regimen. Rescue with leucovorin did not contribute a further significant gain in treatment efficacy, although fewer toxicity-related problems were observed as compared to the no-rescue period. Five prognostic factors emerged as significantly explanatory of the risk of treatment failure in addition to protocol type: lymphocyte count, disease stage, surgical debulking, sex, and nutritional status. Based on these variables, a logistic regression equation could be derived to identify groups that were at risk for treatment failure.

Abdominal Neoplasms↗
PubMed1988

Glutathione monoethyl ester can selectively protect liver from high dose BCNU or cyclophosphamide.

Normal Swiss Webster mice were treated with monocrotaline or high doses of three antitumor alkylating agents (BCNU, cyclophosphamide, or mitomycin C), all of which have been connected with hepatic veno-occlusive disease at our clinic. Prior administration of WR-2721 did not improve the survival of monocrotaline-treated animals. Glutathione (GSH) improved the survival of these animals to a small degree. Glutathione monoethyl ester (GSHet) almost completely protected animals from the toxicity of monocrotaline. Pretreatment with WR-2721 produced moderate increases in survival at the highest doses of BCNU, and at the lower BCNU doses none of the animals pretreated with WR-2721 died before they were killed on day 150. Pretreatment with GSHet gave good protection from BCNU toxicity at the highest dose of the drug, and there were no deaths in the groups of animals treated with GSHet 1 hour before BCNU. On a multiple dose schedule, GSH provided some protection from cyclophosphamide toxicity; GSHet gave a very good level of protection from cyclophosphamide. In none of these treatment groups were lesions suggestive of hepatic or pulmonary venoocclusive disease identified. In all three experimental protocols (monocrotaline, BCNU, and cyclophosphamide), there was a consistent decrease in hepatic toxicity after GSHet pretreatment; this was not observed in GSH- or WR-2721-pretreated animals. There was no evidence of protection of the FSaIIC fibrosarcoma growing in C3H mice as assayed by tumor growth delay or tumor cell survival in groups treated with two different doses of GSHet 1 hour before each drug injection compared to those treated with the BCNU or cyclophosphamide alone, or BCNU with cyclophosphamide. Pretreatment with GSHet did not alter the toxicity of these drugs to bone marrow. GSHet appears to be an effective protector of critical normal tissue and does not appear to protect tumor.

Amifostine↗
PubMed1990

Comparison of etoposide and cisplatin with bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide for salvage treatment in small cell lung cancer. A Southwest Oncology Group Study.

Small cell lung cancer patients who failed primary systemic therapy or who failed after response were randomly assigned to salvage treatment with etoposide (VP-16) and cisplatin (CDDP) or bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide (BTOC). Good risk patients were those who had tolerated prior chemotherapy well, those who had not had prior radiation therapy, and those who were 65 years of age or younger. Patients with a history of poor tolerance, prior radiation therapy, or those who were older than 65 years of age were classified as poor risk. Forty-five patients were randomized to the BTOC regimen and 58 to the VP-16/CDDP regimen. The overall remission rate was 13% (13 of 103 patients). Good risk patients treated with the BTOC regimen had a remission rate of 27% (three of 11 patients), which was the same rate as patients treated with the VP-16/CDDP regimen (three of 11 patients). Poor risk patients had remission rates of 9% (three of 34 patients) with the BTOC regimen and 9% (four of 47 patients) with the VP-16/CDDP regimen. The median survival time from the start of therapy was 16 weeks for all patients. BTOC good risk patients had a median survival time of 10 weeks, as compared with 14 weeks for poor risk patients. VP-16/CDDP good risk patients had a median survival time of 35 weeks, as compared with 12 weeks for poor risk patients. Although based on small numbers, the advantage in survival time for good risk patients treated with VP-16/CDDP over those treated with BTOC is statistically significant. Prior exposure to VP-16 did not influence the outcome of patients treated with VP-16/CDDP. Both regimens produced moderate toxicity, but were generally well tolerated. It was concluded that VP-16/CDDP may be a useful salvage treatment for good risk patients, despite its limited remission rate. Also, it was found that BTOC has no value for patients in this setting and that neither regimen helps patients who are poor risk.

Adult↗
PubMed1990

Platelets acquire a secretion defect after high-dose chemotherapy.

Patients receiving high-dose chemotherapy (HDC) and autologous bone marrow transplantation (ABMT) may experience life-threatening hemorrhagic myocarditis. The authors investigated whether HDC was associated with an acquired platelet defect. Platelet aggregation and release were evaluated after HDC in ten patients with either metastatic breast carcinoma or melanoma. Platelets underwent shape change and a primary wave of aggregation. High-dose chemotherapy was associated with the inhibition of secondary aggregation of platelets induced by adenosine diphosphate (ADP), arachidonic acid, prostaglandin H2 (PGH2) analog (U44619), and collagen. Although electron microscopic study of the platelets revealed normal morphologic features with an adequate number of dense bodies and alpha-granules, release of adenosine triphosphate (ATP) from dense granules was less than 20% of normal. The acquired platelet defect occurred before development of thrombocytopenia. Aggregation of platelets from normal volunteers was not inhibited by either the addition of the chemotherapeutic agents, chemotherapy metabolites, or the patients' sera. In conclusion, HDC induces an acquired abnormality in platelet secretion and aggregation which may contribute to the development of hemorrhagic complications after ABMT.

Adenosine Triphosphate↗
PubMed1990

Autopsy-documented cure of multiple myeloma 14 years after M2 chemotherapy.

Multiple myeloma was diagnosed in a 65-year-old woman in 1974 who thereafter received five-drug M2 chemotherapy. All protein abnormalities subsequently returned to normal and serial bone marrow studies documented complete bone marrow remission. Destructive bone lesions persisted radiographically, but did not progress. In 1987, a localized sigmoid adenocarcinoma was resected. In 1988, the patient presented with multiple brain metastases associated with a primary pulmonary adenocarcinoma that proved rapidly fatal. At autopsy, no evidence of multiple myeloma was found. This report describes the first tissue-documented cure of multiple myeloma 14 years after diagnosis and initiation of M2 chemotherapy. The possible association of multiple myeloma with other malignancies is also discussed.

Aged↗