BACKGROUND: Chemotherapy for metastatic breast cancer is palliative, and the optimal duration of therapy is unknown. We designed a trial to determine whether continuous treatment is superior to stopping treatment after a brief induction period and resuming treatment when the disease progresses. METHODS: We treated 250 women with metastatic breast cancer with six courses of cyclophosphamide, doxorubicin, and fluorouracil given every three weeks. At the completion of this induction period, women whose disease either regressed or remained stable were randomly assigned to receive either continued treatment with cyclophosphamide, methotrexate, and fluorouracil (maintenance therapy) or no further treatment (observation) followed by treatment with cyclophosphamide, methotrexate, and fluorouracil when disease progression became evident (reinduction). RESULTS: The combined rate of complete and partial responses after initial therapy was 30 percent (71 of 233 patients who could be evaluated; 95 percent confidence interval, 25 percent to 37 percent). In another 42 percent (98 patients), the disease remained stable. A total of 145 patients were randomized. Seventy-one were randomly assigned to the maintenance-therapy group, and 74 to the observation group. The median time to progression was 9.4 months for patients in the maintenance-therapy group and 3.2 months for patients in the observation group (P less than 0.001). After reinduction therapy, the median time to progression was 3.5 months. The median length of survival from the time of initial therapy was 14.8 months for all 250 patients; it was 21.1 months for the 71 patients in the maintenance-therapy group and 19.6 months for the 74 patients in the observation group (P = 0.67). Maintenance therapy was the most important determinant of the time before progression (P less than 0.001), but it was not associated with prolonged survival. The changes in performance status were similar in the patients in both groups, but nausea, vomiting, and mucositis were significantly more frequent in the maintenance-therapy group. CONCLUSIONS: In patients with breast cancer who received induction chemotherapy for 18 weeks, subsequent continuous chemotherapy was associated with a significant prolongation of the time before progression as compared with those receiving no further therapy; overall survival, however, was not significantly different in the two groups.

Adult↗

PubMed1991

Thrombolytic therapy soon after left heart catheterization--is it safe?

Puncture of a femoral artery for left heart catheterization is considered a relative contraindication for thrombolytic therapy for some days. We treated 9 patients with systemic thrombolysis who had undergone left heart catheterization in the previous hours. Four patients developed a large hematoma, but only 1 required transfusion. We suggest that thrombolytic therapy can be administered soon after left heart catheterization by the femoral approach, provided that continuous care can be taken over the puncture site.

Adult↗

PubMed1990

Combination high-dose etoposide and vincristine infusion.

Following the identification of a synergistic antitumor effect in a murine model, the combination of etoposide and vincristine has been explored in the clinic. Etoposide was given at 4 dose levels (250, 500, 750 or 1,000 mg/m2) with each dose given in 3 equal fractions daily for 3 days. The dose of vincristine was fixed (two 0.75 mg infusions over 22 hours each between doses of etoposide). A total of 26 patients were entered into study and 7, 11, 10 and 5 patients were treated at the 250, 500, 750, and 1,000 mg/m2 dose levels, respectively. Myelosuppression was the principle side effect and Grade 4 WBC toxicity (less than 1,000/mm3) developed in 14%, 27%, 40% and 40%, respectively, of the patients treated at each of these respective dose levels. Life-threatening infections occurred in 0%, 9%, 30% and 60% of the patients at these levels, respectively. Reversal of marrow toxicity was rapid with repeat courses given at 3-week intervals. Non-hematologic toxicity, including neurotoxicity, nausea, vomiting, and mucositis was generally mild when present. Objective responses were observed in 1 patient each with refractory Hodgkin's disease and immunoblastic lymphoma. Prolonged periods of stable disease occurred in 2 patients with adenocarcinoma of the lung and one patient with Hodgkin's disease. The starting dose of etoposide recommended for further trials of this agent in combination with infusion of vincristine is 500 mg/m2 given in fractionated doses; dose escalation should be possible in many patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Thrombolytic therapy for a patient with systemic lupus erythematosus and acute myocardial infarction.

A young patient with systemic lupus erythematosus was admitted to our hospital because of acute myocardial infarction, and treated by thrombolysis. Coronary angiography revealed a significant stenosis of the left anterior descending artery, together with an intraluminal thrombus. Clotting studies demonstrated an anticoagulant factor suggestive of lupus erythematosus. We conclude that thrombolytic therapy can be useful in patients with systemic lupus erythematosus who present with acute myocardial infarction, although some caution is needed in treatment.

Adult↗

PubMed1990

Interaction of granulocytopenia and construction activity as risk factors for nosocomial invasive filamentous fungal disease in patients with hematologic disorders.

A clinicoepidemiologic study was undertaken to investigate an apparent increase in frequency of nosocomial invasive filamentous fungal disease (NIFFD) in adult patients with acute leukemia hospitalized during a period of hospital construction, and to determine if a relationship existed between the construction activity and the acquisition of NIFFD. The first study goal, to determine the incidence of NIFFD before and during construction, was approached by calculation of incidence rates of NIFFD in patients with acute leukemia, comparing 1982 and 1983 (a baseline period free of construction) to 1986 (a year when construction activity was at its peak). The second study goal, to identify risk factors for the development of NIFFD, was accomplished by reviewing the autopsy records of all patients with underlying hematologic disorders accompanied by granulocytopenia who died in our hospital from 1982 through 1986. Patients with and without autopsy evidence of NIFFD were then compared by univariate and multivariate (logistic regression) analysis to identify potential risk factors for the acquisition of NIFFD. The incidence of NIFFD in patients with acute leukemia hospitalized during the period of hospital construction was significantly increased when compared to a baseline period without construction (11 per 139 versus 4 per 333, p less than .001). Review of all granulocytopenic patients autopsied over the five-year interval 1982 through 1986 revealed duration of granulocytopenia and hospitalization during construction to be risk factors for NIFFD by univariate analysis (p less than .005). Logistic regression showed duration of granulocytopenia to be highly significant independent risk factor (p less than .01) and construction activity to be a probable independent risk factor (p = .09).(ABSTRACT TRUNCATED AT 250 WORDS)

Cross Infection↗

PubMed1990

Vincristine infusion with CHOP-CCNU in diffuse large-cell lymphoma.

Phase I and II trials of vincristine infusion have demonstrated the safety and efficacy of this approach in the treatment of patients with refractory non-Hodgkin's lymphoma. Subsequently, a trial was designed to evaluate this technique in untreated patients. Repeated 5-day infusions of vincristine 0.25 mg/m2 per day were incorporated into a CHOP-CCNU regimen and administered to 24 patients with advanced diffuse large-cell lymphoma. Objective responses occurred rapidly and were observed in 18 (75%) patients in whom 13 (54%) were complete. Toxicity was generally mild to moderate and neurotoxicity appeared to be no worse than typically observed with bolus vincristine. Complete responses have been durable in most patients and 10 (77%) of the complete responders have not relapsed. At this time, 9 (38%) of the total patients remain alive and without evidence of disease from 3.8 to 7.3 years from the start of treatment. One patient died of disseminated gastric cancer at 3.3 years from the start of therapy and there was no evidence of lymphoma at exploratory laparotomy. Infusion of vincristine may be safely incorporated into multiagent chemotherapy programs of the CHOP type for non-Hodgkin's lymphoma. Its potential for protracted nonmyelosuppressive cell kill would appear attractive in designing future trials for this disease.

Adult↗

PubMed1990

[Chronic pericardial effusion due to Toxoplasma gondii in a patient with a myelodysplastic syndrome].

Explore the source record for details and available documents.

Aged↗

PubMed1990

Weight changes in women with metastatic breast cancer treated with megestrol acetate: a comparison of standard versus high-dose therapy.

One hundred seventy-two patients with advanced breast cancer were randomized to receive 160 or 800 mg megestrol acetate per day. Patients were monitored monthly for weight, blood pressure, performance status, edema, measurement of clinically evident lesions, and toxicities. Pretreatment characteristics were similar in both arms. Weight gain was the most commonly seen side effect, with 52% of patients gaining in excess of 10 lb and 28% gaining more than 20 lb. Median weight gain for standard-dose treatment was 5 lb compared with 18 lb for high-dose treatment. There was no dose modification for excessive weight gain in any of the patients receiving the standard dose but doses were modified in 15% of those receiving high-dose megestrol acetate. Weight gains for both groups were analyzed at 30, 90, and 180 days after study entry. Treatment arm, age, prior therapy, response to prior endocrine therapy, race, performance status, dominant disease site, and number of disease sites were included in the analysis. At 30 days, patients taking high-dose megestrol acetate had a mean weight gain of 2.5 lb whereas patients taking the standard dose had stable weights. Factors predictive of weight gain were younger age (P = .0012) and fewer disease sites (P = .017). At 90 and 180 days, patients taking high-dose megestrol acetate had consistently gained more weight than those taking the standard dose (9.0 and 16.0 lb v 2.5 and 9.0 lb, respectively). Significant covariables were treatment arm (P = .0006) and younger age (P = .0211). Probability of gaining 20 lb was dependent only on treatment dose (P = .0002), and median time to a 20-lb weight gain was 217 days. Increases in systolic and diastolic blood pressures were seen in both groups, but the differences were not significant. Megestrol acetate is associated with weight gain in women with advanced breast cancer, and the amount of weight gained correlates directly with dose of megestrol acetate, length of treatment, and age of patient.

Blood Pressure↗

PubMed1989

Phase I study of vincristine and escalating doses of etoposide.

A phase I trial of vincristine and etoposide was designed following the identification of a potentially synergistic antitumor effect in a murine model. The dose of vincristine was fixed (0.5 mg daily for 3 days). Etoposide was given at 1 of 3 total dose levels (250, 500, or 750 mg/m2) per treatment. Each dose was given in 3 equal fractions and each fraction was given daily for 3 days, i.e., 83.3 mg/m2/d x 3d, 166.7 mg/m2/d x 3d, or 250 mg/m2/d x 3d. A total of 31 patients were entered into study including 10, 18, and 3 patients treated at the 250, 500, and 750 mg/m2 dose levels, respectively. Dose-limiting toxicity occurred at the 750 mg/m2 level, in which Grade 4 myelosuppression developed in all of the patients. Life-threatening gram negative sepsis occurred in two of these patients and both required platelet transfusions. Grade 3-4 WBC toxicity was observed in 9 of 16 (56%) evaluable patients treated at the 500 mg/m2 level, but reversal of toxicity was generally rapid with repeat courses given at 3 week intervals in most patients. Non-hematologic toxicity was negligible. Objective responses were observed in 2 of 4 patients with Hodgkin's disease. The starting dose of etoposide recommended for phase II trials of this agent in combination with vincristine is 500 mg/m2; dose escalation may be possible in some patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

Infusion of etoposide and vincristine in non-Hodgkin's lymphoma.

Infusion of etoposide has previously been evaluated in phase I trials. Vincristine (VCR) given by infusion has been shown in a phase II trial to be active in some cases of non-Hodgkin's lymphoma despite prior exposure to bolus VCR. Infusion of etoposide and the combination of VCR infusion with etoposide (given either as an infusion or bolus) were evaluated in 24 patients with previously treated non-Hodgkin's lymphoma. Five-day infusions of etoposide alone (n = 10), both etoposide and VCR (n = 9), or VCR with bolus etoposide (n = 5) were evaluated. Partial responses were observed in 0, 2 (22%), and 1 (20%) of the patients, respectively. Myelosuppression was the principal toxicity with the 5-day infusions of etoposide alone and with the double infusion combination, but was mild in the VCR infusion coupled with etoposide bolus. Non-hematologic toxicity was mild to moderate in each. For patients with refractory non-Hodgkin's lymphoma, the infusion of etoposide with or without VCR infusion appeared to offer no advantage over bolus administration of etoposide or infusion of VCR alone.

Adolescent↗

PubMed1989

The safety of dental extractions in patients with hematologic malignancies.

Dental disorders have been recognized as major sources of infection in patients with hematologic malignancies (HM). Management of severe dental infections usually includes dental extractions (DE), but the safety of extractions in patients with HM who are at risk for bleeding, sepsis, and poor wound healing has not been well established. In conjunction with an aggressive program of dental care, 142 DE were performed in 26 patients with acute leukemia, myelodysplastic syndromes, and myeloproliferative disorders. Granulocytopenia (less than 1,000 granulocytes/microL) was present during or within ten days following surgery in 14 patients. In these 14 patients (101 DE), the mean granulocyte count was less than 450/microL, with a median duration of granulocytopenia following surgery of 32 days (range, four to 169 days). Thrombocytopenia (less than 100,000 platelets/microL) occurred during or within two days following surgery in 13 patients (80 DE), with a mean platelet count of 63,500/microL. Transfusions were given for platelet counts less than 50,000/microL. All DE were performed without significant complications. Bleeding was minor to moderate and easily controlled with local measures; no patient required transfusion due to hemorrhage. Average maximum temperature 24 hours after DE was 37.7 degrees C. No episodes of bacteremia were documented within ten days of DE. Minor delay in wound healing was observed in two patients. We conclude that DE can be safely performed in patients with HM in combination with aggressive supportive care.

Agranulocytosis↗

PubMed1989

[Fatal acute myocardial infarct in a 14-year old boy].

The case of a 14 year old male, with no personal or family antecedents of ischemic heart disease, who died owing to an acute myocardial infarct into the few hours of beginning to pain. In the necroscopic study it was observed that the coronary arteries did not show any anatomical alterations or stenosis from their origins, although a microscopic study revealed extensive zones of necrosis.

Adolescent↗

PubMed1988

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↗