The breast cancer prevention trial: a correction.
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Breast Neoplasms↗
Biomedical subjects
J N Atkins
Publications and source records attributed to J N Atkins.
Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study.
PURPOSE: To determine in a prospective randomized trial whether high-dose orally administered medroxy-progesterone acetate (MPA) was superior to tamoxifen in patients with recurrent or metastatic breast cancer who had received no prior endocrine therapy in either the adjuvant or advanced setting. PATIENTS AND METHODS: Patients initially received either tamoxifen 20 mg/d orally or MPA 1 g/d orally. At the time of disease progression, patients were crossed over to the other regimen. Eligibility required patients to be age > or = 18 years, performance status 0 to 3, and estrogen receptor (ER)- or progesterone receptor (PR)-positive or unknown. RESULTS: One hundred eighty-two eligible patients were entered and 166 were assessable for response. Complete plus partial response rates for tamoxifen and MPA were 17% and 34%, respectively (P = .01). Patients with bone metastases had a significantly higher partial response rate with MPA compared with tamoxifen (33% v 13%). Median time to treatment failure was 5.5 months for tamoxifen and 6.3 months for MPA (P = .48). The median survival duration was 24 months for tamoxifen and 33 months for MPA (P = .09). Multivariate analysis showed that treatment significantly influenced response rate, but not time to treatment failure or survival. After treatment failure following MPA, six of 42 patients (14%) treated with tamoxifen responded, compared with six of 49 (12%) treated with MPA following tamoxifen. Both agents were associated with minimal toxicity, but 35% of patients on MPA gained more than 20 lb as opposed to only 2% on tamoxifen. CONCLUSION: In this trial, initial treatment with MPA of endocrine-naive metastatic breast cancer patients was associated with a significantly higher response rate but not with improvement in time to treatment failure or survival, when compared with initial treatment with tamoxifen. Further randomized trials in patients with bone metastases are warranted to determine if high-dose progestin therapy is superior to tamoxifen in these patients.
Administration, Oral↗
High-dose 24-hour infusion of 5-fluorouracil in metastatic prostate cancer. A phase II trial of the Piedmont Oncology Association.
Thirty-two patients with metastatic carcinoma of the prostate refractory to endocrine therapy were entered on trial. No patient entered in the study had prior chemotherapy. Patients were treated with 5-fluorouracil given at a dosage of 4 gm/m2 over a 24-hour period every 2 weeks. Of the 27 patients evaluable for response, there were no complete or partial remissions, but 9 (33%) had a stable disease. The 95% confidence interval for complete and partial response in this series (0 of 27 patients) is 0.0-12%. Myelosuppression and gastrointestinal toxicity was moderate. Two patients, however, experienced major but completely reversible neurotoxicity, including 1 with cerebellar ataxia and 1 with memory loss and stroke-like symptoms. These data indicate that high-dose fluorouracil used in this dosage and schedule is ineffective in the therapy of advanced carcinoma of the prostate.
Adenocarcinoma↗
A phase II trial of high-dose cytarabine and cisplatin in previously untreated non-small cell carcinoma of the lung. A Piedmont Oncology Association Study.
Thirty-seven chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC) were treated with cytarabine (3 g/m2 intravenously [IV] during 3 hours) after IV bolus cisplatin (100 mg/m2 repeated every 3 weeks). Aside from nausea and vomiting, the principal toxicity was hematologic, with Grade IV myelosuppression in 32% and Grade III in 14%. Four patients died while on study. One complete and four partial responses were observed for an overall response rate of 14%. Responses were limited to lymph node and lung metastases and occurred in two of 17 adenocarcinomas, two of 12 squamous cell carcinomas, and one of eight large cell carcinomas. At this dose, the plasma level of cisplatin is only 3 micrograms/ml and the plasma level of cytarabine is 10 to 50 micrograms/ml, compared with the levels of 10 micrograms/ml and 1000 micrograms/ml, respectively, required for in vitro synergy. The severity of myelotoxicity observed indicates that, even at these levels, cisplatin enhances cytarabine activity. The combination may prove useful in malignancies that are sensitive to cytarabine, but is not of benefit in cytarabine-resistant malignancies such as NSCLC.
Adult↗
Amelioration of vincristine neurotoxicity by glutamic acid.
Neurotoxicity is the principal limiting side effect of the widely used antitumor agent, vincristine. Following evaluation of glutamic acid as a potential modifier of vincristine toxicity in preclinical studies in mice and a preliminary clinical trial, a prospective, double-blind, placebo-controlled, randomized trial was conducted by the Piedmont Oncology Association. Of 87 patients entered into the study, 84 were evaluable, including 42 patients who were randomly assigned to receive vincristine 1.0 mg/m2 weekly for six doses and 42 patients who were assigned to receive glutamic acid 500 mg orally three times daily plus vincristine. The following neurotoxic signs and symptoms were evaluated before each dose of vincristine: reflex changes, paresthesias, constipation, strength, and mental changes. Loss of the Achilles tendon reflex, an objective parameter, was noted in 19 percent of patients receiving glutamic acid and 42 percent of control subjects (p = 0.03). Development of moderate to severe paresthesias, a subjective parameter, occurred in 19 percent of the glutamic acid group and 36 percent of the placebo group (p = 0.09). Overall moderate neurotoxicity (6 units or more), determined by adding the grade of each neurotoxic parameter for the weekly clinic visit in which maximum neurotoxicity occurred, was observed in 21 percent of patients receiving glutamic acid and 43 percent of those in the control group (p = 0.04). Hematologic and gastrointestinal side effects occurred with similar frequency in the two groups. The administration of glutamic acid has decreased vincristine-induced neurotoxicity without any attendant side effects.
Adult↗
Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies.
Cytosine arabinoside (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m2 as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9-12 and 21-24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m2 X 2 doses of ara-C and 50 mg/m2 of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.
Adult↗
Phase II trial of high-dose cytarabine and cisplatin in locoregional previously untreated squamous carcinoma of the head and neck: a Piedmont Oncology Association Study.
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Aged↗
Clinical trial of pyridoxine to reduce vincristine neurotoxicity.
In a murine model system, pyridoxine has demonstrated protective properties during administration of lethal doses of vincristine (VCR). Subsequently, pyridoxine has been evaluated in patients receiving VCR during an adjuvant chemotherapy program for stage II carcinoma of the breast. The toxicities, cumulative VCR dosage, and percentage of ideal dosage observed in 24 patients receiving pyridoxine have been compared to those observed in 88 patients who previously received VCR without pyridoxine in the same chemotherapy program. All patients ideally were to receive VCR 1.0 mg/m2 weekly for 6-weeks with dose modification for neurotoxicity. Treatment patients received pyridoxine 1.5 grams p.o. daily in three divided doses during the 6-week course. The degree of neurotoxic manifestations of VCR was similar in the treatment and comparison patients. Absent to mild neurotoxicity was observed in approximately 70% of patients in both groups; moderate or greater neurotoxicity occurred in about 30% of patients in both groups. Full dosage (6.0 mg/m2) was attained in 8 (33%) treatment patients and 18 (24%) comparison patients (p = 0.28). The mean percentage of ideal dosage of VCR was 84.6 +/- 10.8 in patients receiving pyridoxine and 81.9 +/- 21.6 in those given only VCR (p = 0.59). Gastrointestinal and hematologic toxicities were similar in both groups. Pyridoxine in this dose and schedule afforded no protection from the neurotoxic side effects of VCR.
Adult↗
Phase II trial of vincristine infusion in acute leukemia.
A phase II trial of prolonged IV infusions of vincristine was conducted in 21 patients with refractory acute leukemia. Patients received 0.25-0.50 mg/m2 by infusion daily for 5 days after an initial 0.5-mg bolus. A partial response was observed in one of two patients with acute lymphoblastic leukemia. Of 14 patients with acute nonlymphoblastic leukemia, a complete response lasting for 2.5 months occurred in one patient and a partial response lasting 1.3 months was observed in a second. No objective responses were noted in five patients with blast crisis of chronic granulocytic leukemia. Nonhematologic toxicity was minimal and, when present, generally consisted of a feeling of weakness; constipation, mucositis, and areflexia were also observed. Hematologic toxicity consisted mainly of mild to moderate reduction of platelets in most patients; marked thrombocytopenia (less than 50,000/mm3) occurred in two patients whose pretreatment platelet count was greater than 100,000/mm3. Although generally well tolerated, prolonged infusion of vincristine appears to have limited activity in the treatment of refractory acute nonlymphoblastic leukemia and blast crisis of chronic granulocytic leukemia; further evaluation is needed in acute lymphoblastic leukemia refractory to conventional bolus injection.
Acute Disease↗
Sequential hemibody and local irradiation with combination chemotherapy for small cell lung carcinoma: a preliminary analysis.
Sequential hemibody irradiation (SHB) was integrated with combination chemotherapy and local irradiation (LRT) in the induction and consolidation phases of a therapeutic protocol for small cell lung carcinoma (SCLC). Forty-one previously untreated patients were entered into this program. Among 38 evaluable patients (20 with limited disease [LD] and 18 with extensive disease [ED], the overall response rate was 63% (90% in LD and 33% in ED patients). The estimated overall survival is 8.1 months. The major toxicity has been myelosuppression--especially thrombocytopenia. The frequency of previously described "acute radiation syndromes" and radiation pneumonitis associated with hemibody irradiation have been substantially decreased at the current dosage with premedication and shielding techniques. The integration of SHB as a systemic therapy with combination chemotherapy and LRT is a feasible program for sequential administration of non-cross-resistant agents in SCLC and may be beneficial in patients with limited disease.
Adult↗
Schistocytes in erythroleukemia.
A patient whose initial hematologic evaluation suggested the diagnosis of a microangiopathic hemolytic anemia (MAHA) was further evaluated and found to have erythroleukemia (DiGuglielmo's syndrome). This prompted us to review retrospectively the peripheral blood morphology of 12 patients with erythroleukemia. Anisocytosis, poikilocytosis, macrocytosis, and nucleated red cells have been described in patients with erythroleukemia; however, changes characteristic of a microangiopathic hemolytic process (schistocytes) have not been previously described. Our patients with erythroleukemia had prominent helmet and fragmented red cells, as well as elliptocytosis. Six of our 12 patients with erythroleukemia did not have blasts on their peripheral smear, and platelets were decreased (platelet count ranged from 2 to 92 X 10(3)/microliter), resulting in changes similar to patients with MAHA due to thrombotic thrombocytopenic purpura (TTP), traumatic RBC lysis, and disseminated intravascular coagulation. Our data indicate the RBC changes characteristic of MAHA are commonly seen in erythroleukemia, and that as many as half of these patients may not have white cell changes suggestive of leukemia on the peripheral smear. Patients presenting with microangiopathic hemolytic anemia require a bone marrow examination to confirm or exclude a myelodysplastic syndrome.
Aged↗
Fluorouracil and the palmar-plantar erythrodysesthesia syndrome.
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Dermatitis, Exfoliative↗
Platelet-aggregating factor in thrombotic thrombocytopenic purpura.
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Agglutination Tests↗
Phase I trials of high-dose cytosine arabinoside (HDara-C) and HDara-C plus cisplatin in patients with advanced malignancies.
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Adult↗
Maternal plasma concentration of pyridoxal phosphate during pregnancy: adequacy of vitamin B6 supplementation during isoniazid therapy.
Vitamin B6 is an important supplement both for pregnant patients and for those receiving isoniazid. Therefore, we decided to monitor pyridoxal phosphate (PLP) concentrations in 12 pregnant patients who were receiving isoniazid to be certain that supplementation was adequate. Patients were given a prenatal vitamin preparation and 50 mg of pyridoxine hydrochloride daily. At 1 month 10 of the 12 patients had adequate PLP concentrations. Seven of these 10 patients had elevated PLP concentrations and 3 had normal concentrations. Supplementation with 52 to 60 mg per day of Vitamin B6 produces adequate PLP concentrations in pregnant patients who are also taking isoniazid.
Female↗
Reye's syndrome in the adult patients.
Reye's syndrome has been thought to represent a childhood illness. Our thesis is that it is a postviral systemic disease which may affect adults as well. A 51 year old woman is presented whose case meets all of the major criteria for Reye's syndrome. The diagnostic criteria for Reye's syndrome are summarized, and two other reported cases of Reye's syndrome in adults are reviewed. The diagnosis of Reye's syndrome in adults requires familiarity with the diagnostic criteria and a "high index of suspicion."
Female↗
Phase I study of high-dose cytarabine and cisplatin in patients with advanced malignancy.
Nineteen patients with advanced malignancy participated in a phase I trial of high-dose cytarabine (ara-C) and cisplatin in combination. Dose and schedule were based on laboratory data indicating synergy for concurrent use of these drugs. Cisplatin (100 mg/m2) was administered during the 2nd and 3rd hours of a 3-hour ara-C infusion. The ara-C dose was escalated in subsequent patients following a starting dose of 1 g/m2. Two brief responses were noted. The study was terminated prematurely due to protracted (several weeks) nausea, occasional vomiting, and severe lassitude.
Adult↗