Search PubMed⌕ Search

Biomedical subjects

B L Powell

Publications and source records attributed to B L Powell.

At least 55 records · Page 3Linked to original sources
PubMed1990

High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association.

One hundred seventy-two patients with advanced breast cancer were randomized to receive oral standard-dose megestrol acetate (MA), 160 mg/d or high-dose MA, 800 mg/d. All but two patients had one prior trial of tamoxifen therapy for either metastatic disease (74%) or as adjuvant treatment (26%). Pretreatment characteristics were similar for both arms. High-dose MA resulted in a superior complete plus partial response rate (27% v 10%, P = .005), time to treatment failure (median, 8.0 v 3.2 months, P = .019), and survival (median, 22.4 v 16.5 months, P = .04) when compared with standard-dose therapy. These differences remained significant after adjustment for other covariates. Thirty-four patients were given high-dose MA after failure of standard-dose MA treatment, and none responded. Weight gain was the most distressing side effect, with 13% of standard-dose and 43% of high-dose patients gaining more than 20 lbs. Four major cardiovascular events occurred in patients receiving high-dose treatment and one in patients given standard doses. Other toxicity was modest. High-dose MA may represent a significant improvement in secondary endocrine therapy for advanced breast cancer patients refractory to initial endocrine treatment, but its use on a regular basis should be reserved until these results are confirmed by other clinical trials.

Adult↗
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

Correlation of the proliferative index of residual leukemia with outcome in patients treated with sequential high dose ara-C and asparaginase.

Therapy of acute myelogenous leukemia (AML) with sequential high-dose ara-C and asparaginase (HiDAC----ASNase) on a day 1 and 8 schedule was designed to exploit potential recruitment of residual leukemia cells following initial cytoreduction from day 1 treatment. DNA flow cytometry was used to evaluate the proliferative index (%S + G2M) of bone marrow leukemia cells from pretreatment and day 8 marrow samples. The proliferative index on day 1, day 8, and incremental change (day 8 minus day 1) were analyzed for their correlation with bone marrow aplasia on day 15 and with the attainment of subsequent complete remission. Pretreatment (day 1) and the change in proliferative index did not correlate (p greater than 0.10) with day 15 marrow aplasia or with clinical outcome. However, the magnitude of the day 8 proliferative index did relate to the attainment of bone marrow aplasia on day 15 (p = 0.05) and the attainment of complete remission (p = 0.002). Recruitment of residual leukemia cells into the proliferative phases of the cell cycle may contribute to the unique efficacy of the day 1 and 8 schedule of HIDAC----ASNase. Additionally, the cytokinetics of residual leukemia after initial chemotherapy may be predictive of outcome and could be useful as a marker for the design of optimal therapeutic regimens.

Adolescent↗
PubMed1989

Mitoxantrone and high-dose ara-C in refractory malignancies: a phase I trial.

On the basis of in vitro studies demonstrating marked synergy between mitoxantrone and high-dose cytosine arabinoside (ara-C) (HiDAC) against L5178Y murine leukemia and clinical studies showing usefulness of the combination in patients with refractory acute myeloid leukemia, a phase I study was initiated to find tolerable doses for use in patients with refractory solid tumors. Initial dose levels were mitoxantrone 2 mg/m2 infused over 30 minutes, followed by high-dose ara-C 750 mg/m2 infused over 3 hours repeated once at 24 hours (total dose 4 mg/m2 mitoxantrone and 1,500 mg/m2 HiDAC per 2-day course), with planned subsequent escalation of mitoxantrone. Moderate-to-severe myelosuppression, however, required sequential dose reduction of both agents. Nonhematologic toxicity was restricted to manageable nausea and vomiting in one-half the patients and a single episode of transient delirium of uncertain etiology. No responses were observed in 23 heavily pretreated patients with a wide variety of malignancies. On the basis of this study, doses of 187-375 mg/m2 ara-C given every 24 hours for two doses following mitoxantrone 1 mg/m2 every 24 hours for two doses would be tolerated by most patients with subsequent dose escalation in some as allowed by myelosuppression.

Adult↗
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

Low-dose ara-C therapy for acute myelogenous leukemia in elderly patients.

Forty-four evaluable patients with untreated acute myelogenous leukemia received twice-daily subcutaneous injections of low-dose ara-C (10 mg/m2) for less than or equal to 42 days. The median age was 72 years (range 53-87); 42 of 44 patients were greater than or equal to age 60. Ten patients (23%) had complete responses with a median duration of 9.9 months. Median survival was 3 months (range 0.6-31.2+) for all patients, and 19.5 (range 7.9-31.2+) for patients who attained complete responses. Cytoreduction occurred slowly with low-dose ara-C and five of ten patients who achieved complete remission did not develop marrow aplasia. Toxicity was predominantly related to infections associated with granulocytopenia. Nonhematologic toxicity was limited. Low-dose ara-C as used in this trial results in a complete response rate and a duration of response similar to those achieved with other treatments in elderly patients, but with reduced toxicity.

Aged↗
PubMed1988

Phase I-II trial of acivicin in adult acute leukemia.

Six patients with relapsed or refractory acute leukemia were treated with 9 mg/m2 or 11 mg/m2 of acivicin daily for seven days in a phase I-II trial. No responses were attained and further dose escalation was prohibited by neurotoxicity in 2 of 3 patients who received 11 mg/m2/day. Although acivicin appears to have limited potential as a single agent, laboratory evaluation of leukemic blasts in one patient revealed cell cycle (S-phase accumulation) and metabolic effects which suggest that acivicin may be effective as a modulator of other antileukemia agents such as cytosine arabinoside.

Aged↗
PubMed1988

Translocation (8;16)(p11;p13) in patients with acute monocytic leukemias. An evolving syndrome?

The case of a patient with a t(8;16)(p11;p13) chromosomal abnormality and acute myelomonocytic leukemia is described. Review of cases with this translocation showed that 11 of 13 patients had acute monocytic or myelomonocytic leukemia with a high frequency of extramedullary disease and phagocytosis of normal blood cells by the malignant cells. While these patients are not clinically distinct from others with acute monocytic leukemia, the characteristic features of this subset of patients will certainly evolve.

Adolescent↗
PubMed1988

Phase II trial of high-dose cytosine arabinoside and cisplatin in recurrent squamous carcinoma of the head and neck. A Piedmont Oncology Association Study.

Fifteen patients with recurrent squamous carcinoma of the head and neck received high-dose cytosine arabinoside (ara-C) (3 g/m2) and cisplatin (100 mg/m2) every 3 weeks in an attempt to explore the dose-dependent synergy between these two agents. A partial response was attained in one patient; there were no complete responses. The major toxicity was myelosuppression. With the current schedule, high-dose ara-C failed to improve the response rate achieved with cisplatin alone.

Adult↗
PubMed1988

Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association.

One hundred thirty-eight patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally four times daily or tamoxifen 10 mg orally twice a day. Upon treatment failure patients were crossed over to the alternate treatment. Eligibility required that either the estrogen receptor (ER) or progesterone receptor (PR) be positive or that both values be unknown, and that the patients be at least 2 years post-spontaneous menopause or over 50 years of age. Pretreatment characteristics including performance status (PS), disease-free interval (DFI), receptor status, and prior treatment were similar for both groups. Only three patients had previous hormonal therapy while one third had prior chemotherapy. Objective response was determined using strict International Union Against Cancer (UICC) criteria. Seventeen of 61 patients achieved complete response (CR) or partial response (PR) on megestrol (28%) while 20 of 64 patients achieved CR or PR on tamoxifen (31%). Responses of skin and bone lesions were similar for both agents; however, more patients with visceral disease responded to tamoxifen. Response did not correlate with the level of ER or PR but was correlated with age. Both unadjusted and adjusted analysis of time to progression and adjusted analysis (for pretreatment variables) of survival showed significant differences favoring tamoxifen. Six of 44 patients (14%) crossed from megestrol to tamoxifen achieved CR or PR while only two of 38 patients (5%) crossed from tamoxifen to megestrol achieved response. Only one of the original patients randomized to megestrol remains on study, while 12 patients still remain on tamoxifen. These data indicate similar response rates for megestrol and tamoxifen; however, time to progression and overall survival significantly favor tamoxifen when used as first-line therapy in this trial.

Adult↗
PubMed1988

Improvement of long-term survival in extensive small-cell lung cancer.

The effect of adding the epipodophyllotoxin etoposide (VP-16-213) to a standard chemotherapy regimen for patients with extensive stage small-cell lung cancer was evaluated during a randomized trial. Chemotherapy consisted of vincristine, doxorubicin, and cyclophosphamide (VAC) alone or with etoposide (EVAC). Of 139 patients enrolled, 136 patients were eligible for study and all but five were evaluable for response. The overall objective response was 46% in the VAC group v 70% in the etoposide-treated group (P = .008) with complete response (CR) rates of 12% v 29%, respectively (P = .030). Although the time to the observation of disease progression was significantly longer in the group of patients receiving etoposide (9.6 v 6.5 months, P = .010), overall survival was similar; this was probably due to administration of other agents including etoposide at the time of VAC failure. However, there were noteworthy differences in long-term (greater than or equal to 2 year) survival. Whereas only four (6%) patients treated with VAC lived 2 years, 11 (16%) of the etoposide-treated group did so (P = .100). Two-year failure-free survival was attained in one (2%) of the VAC patients and eight (11%) of the patients treated with etoposide (P = .034). Long-term survivorship, heretofore usually reported in patients with limited stage disease after a variety of treatments, may be possible with this drug combination in the setting of extensive disease.

Adult↗
PubMed1988

Low dose Ara-C for patients with myelodysplastic syndromes.

Forty patients with high risk myelodysplastic syndromes--refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or chronic myelomonocytic leukemia--were treated with subcutaneous low dose cytosine arabinoside, 10 mg/m2 twice daily for up to 42 days. In 38 evaluable patients there were nine (24%) complete and four (11%) partial responses. Response was associated with symptomatic improvement and resolution of the need for red cell and platelet transfusions. The median duration of complete response was 9.8 months (range, 2.4-17.9); these patients had a median survival of 15.7 months (range, 6.0-22.7). Toxicities were predominantly those associated with pancytopenia, i.e., infection and hemorrhage.

Adult↗
PubMed1987

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↗
PubMed1987

The management of nausea and vomiting in clinical oncology.

The development of cisplatin and the use of intensive combination chemotherapy have resulted in significant therapeutic advances in medical oncology, as well as the need for intensive supportive care aimed at ameliorating enhanced toxicity. From the patient's perspective, the most prominent adverse effects of chemotherapy are nausea and vomiting. Inadequate control of these symptoms leads to physiologic debilitation and psychologic distress, sequelae that result in either the patient being medically unable to continue therapy or noncompliant. Recent antiemetic research has created a voluminous data base from which the appropriate management of many aspects of chemotherapy-induced emesis can be gleaned. Despite these advances, at least 30% of patients continue to experience some degree of acute emesis with chemotherapy, and the problems of delayed and anticipatory nausea and vomiting have just begun to be addressed. Effective management of chemotherapy-induced emesis is an important aspect of the total care of oncologic patients, improving patient compliance and enhancing the therapeutic index of chemotherapy regimens resulting in a decrease in the overall morbidity and mortality of cancer therapy.

Antiemetics↗
PubMed1987

Adjuvant chemotherapy of solid tumors.

Adjuvant chemotherapy for microscopic disease following eradication of clinically detectable lesions by primary surgery and/or radiotherapy is of documented benefit for some oncology patients. However, for many primary cancers efficacy is limited to specific subgroups of patients or has demonstrated no advantage over primary therapy alone. The rationale for adjuvant chemotherapy and results of selected trials are reviewed. In patients for whom adjuvant therapy is of demonstrated benefit, further trials aimed at delineation of patient selection factors, optimal chemotherapy regimens and schedules, and duration of therapy are needed; progress in adjuvant treatment of other subgroups may require development of more effective antineoplastic drugs, in addition to exploration of these factors.

Breast Neoplasms↗
PubMed1987

Antiemetic therapy in patients treated with high-dose cytosine arabinoside.

The antiemetic efficacy of metoclopramide (MCP) was evaluated in 33 consecutive patients treated with high-dose cytosine arabinoside (HiDAC), greater than or equal to 3 g/m2, a highly emetogenic agent increasingly used in patients with hematologic malignancies for which no previous formal antiemetic trials have been reported. Administration of MCP in conjunction with prophylactic diphenhydramine resulted in major antiemetic responses (0-2 episodes of emesis in the 24 h after therapy) in 23 of 33 (70%) patients. The addition of lorazepam (LZP) to MCP resulted in major antiemetic response in 7 or 8 (88%) patients who failed to respond to MCP alone. Major side effects were extrapyramidal reactions (5%) and moderate diarrhea (18%). MCP alone or in conjunction with LZP is effective antiemetic therapy in patients treated with HiDAC.

Adolescent↗