Biomedical subjects

H B Muss

Publications and source records attributed to H B Muss.

At least 91 records · Page 5Linked to original sources

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

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↗

PubMed1990

Methotrexate in advanced endometrial carcinoma. A phase II trial of the Gynecologic Oncology Group.

Thirty-three patients with advanced or metastatic endometrial carcinoma were entered in a Phase II trial utilizing methotrexate, 40 mg/m2 intravenously on a weekly basis. Almost all patients had prior total abdominal hysterectomy and almost two-thirds prior pelvic irradiation. No patient had prior chemotherapy. There was one complete and one partial response, for a complete and partial response rate of 6% (95% confidence intervals for a response of 1.7 to 19.6%). Toxicity was mild, with major adverse effects being nausea and vomiting and myelosuppression. One death may have been drug related. Methotrexate displays minimal clinical activity in patients with advanced or recurrent endometrial carcinoma who have received no prior chemotherapy.

Adult↗

PubMed1989

The relation of flow cytometry to clinical and biologic characteristics in women with node negative primary breast cancer.

Flow cytometry (FC) analysis including DNA index (ploidy status) and cell kinetics (%S and %S + G2/M) was done on frozen tissue of the primary lesions of 101 women with node negative (N-) breast cancer who were studied prospectively. Currently, 19% (19/101) of the patients have recurred. No significant relations have been found between recurrence or survival and age, estrogen/progesterone receptor status, tumor size, and tumor type. The DNA index (ploidy) was not related to any clinical variable, time to recurrence, or survival. Aneuploid tumors did, however, have significantly higher %S phase activity. Patients with %S activity less than or equal to the median value were significantly different from those patients with %S above the median. They were older and had a higher frequency of ER/PR positive and well- or moderately differentiated tumors. Patients with %S + G2/M greater than the median value showed shorter time to recurrence (P = .055) and shorter survival (P = .006), whereas %S alone was significantly associated only with survival. Multivariate analysis showed that neither DNA index nor cell kinetics was significantly associated with time to relapse. DNA index was not significantly associated with survival; %S was of borderline significance whereas %S + %G2/M was a significant independent predictor of survival. Although FC data may provide independent information related to survival in N-women, additional research in a larger number of patients is needed to define its precise role in patient management.

Breast Neoplasms↗

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

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

Megestrol acetate in breast cancer--a panel discussion.

Physicians have been using hormonal manipulation to treat advanced breast cancer for almost a century. Surgical ablation of the ovaries, adrenals, and pituitary glands has achieved remarkable tumor regression in sensitive patients. Alternatively, large doses of estrogens, progestins, and androgens have achieved similar results. More recently, the emergence of new therapies, such as antiestrogens, LHRH agonists, and chemical blockade of adrenal steroid biosynthesis offer additional choices. Within limits, all of these therapies are equally effective in sensitive patients. The trend at the present time is to select a therapy that will produce a good response with minimal toxicity. Here the participating physicians will discuss one such therapy-Megace (megestrol acetate). They will consider the role of Megace in the treatment of advanced breast cancer along with issues such as toxicity, dose response, etc.

Breast Neoplasms↗

PubMed1989

Concurrent chemotherapy and single high-dose plus whole abdominopelvic radiation for persistent ovarian carcinoma.

Twenty-two patients were treated with concurrent single high-dose and standard fractionated abdominopelvic radiation and chemotherapy (cisplatin or hexamethylmelamine). Those who had prior cisplatin received hexamethylmelamine and radiation (16 patients) while those without prior cisplatin received cisplatin and radiation (6 patients). The primary aim of the study was to assess the tolerance and effectiveness of concurrent radiation and chemotherapy in patients who had failed prior chemotherapy. All patients experienced mild to moderate nausea, vomiting, and diarrhea. Hematologic adverse effects were minimal. Three patients requiring laparotomy for radiation induced small bowel obstruction had confirmed complete responses but 2 died acutely of treatment-related complications without evidence of tumor. In the 15 patients with suboptimal disease (greater than 1 cm residual disease) prior to the study, only 1 had a complete response while 2 of 7 optimal patients (less than or equal to 1 cm residual disease) had a complete response. All 3 complete responders received cisplatin and 2 had 1 cm or less of residual disease prior to the study. In the hexamethylmelamine group 3 of 16 patients had a partial response. Concurrent single high-dose whole abdominopelvic radiation and cisplatin may be effective in patients with minimal disease (less than or equal to 1 cm); however, radiation-associated bowel complications were severe.

Abdomen↗

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

Mitoxantrone in the treatment of advanced vulvar and vaginal carcinoma. A gynecologic oncology group study.

Nineteen evaluable patients with advanced carcinoma of the vulva or vagina were treated with mitoxantrone, 12 mg/m2, every 3 weeks. All patients had good performance status and measurable disease and only nine had received prior chemotherapy. No complete or partial responses were noted. The major toxicity was myelosuppression; other toxicity was mild, and no cardiac toxicity or drug deaths occurred. The median progression-free interval was 1.3 months for patients with vulvar cancer and 1.6 months for patients with vaginal cancer. Median survival was 3.2 months for patients with vulvar cancer and 2.7 months for patients with vaginal cancer. Mitoxantrone displays no activity in patients with advanced carcinoma of the vulva or vagina.

Adult↗

PubMed1989

Relationship between mammographic features and hormone receptor content in patients with breast cancer.

Recurrences of breast cancer are more responsive to hormone therapy if the tumors are positive for estrogen receptors or progesterone receptors. To assess the relationship between hormone receptor content, mammographic tumor morphology, and breast parenchymal patterns, we reviewed charts and mammograms of 210 patients with primary unilateral breast cancer. Mammograms of tumors in 97 patients were divided morphologically into five groups: (1) spiculated mass, (2) architectural distortion, (3) calcifications only, (4) circumscribed mass, and (5) tumor not visible. Estrogen receptor positivity was 81% (39/48) in group 1, 37% (7/19) in group 2, 17% (2/12) in group 3, 31% (4/13) in group 4, and 60% (3/5) in group 5 (P less than .001). Mean estrogen receptor content was also significantly different among groups (P less than .001). There was no statistically significant association between tumor morphology and progesterone receptors, or between calcifications and receptor status. In all 210 patients, hormone-receptor-positive tumors showed no association with mammographic parenchymal pattern. When direct assay of estrogen receptors is unavailable, mammographic appearance of the tumor may suggest the estrogen receptor status.

Breast Neoplasms↗

PubMed1989

Chemoinfusion of the hepatic artery for metastases to the liver.

During a five year period, 69 patients were treated for carcinoma of the liver (seven primary tumors and 62 metastatic tumors) with 5-fluorodeoxyuridine (5-FUDR) administered through a hepatic artery (n = 62) or portal vein (n = 3) implantable infusion pump. Ten patients proved to have previously unsuspected extrahepatic nodal metastases at laparotomy for pump insertion. 5-FUDR was given in 14 day cycles for three months. At the end of that period and at three month intervals thereafter (mean follow-up time of 18 months, a range of one to 60 months), patients were evaluated with roentgenograms of the chest, liver function tests, carcinoembryonic antigen levels, radionuclide scans and computed tomography. Thirty-five patients had a partial response, nine had stabilization of the disease and 25 had progression of the disease (five during therapy, who were given mitomycin C). Median regression was 6.8 months (a range of three to 18 months). Six of the 35 partial responders, three of the nine patients with stabilization and ten of the 25 patients with progression had extrahepatic visceral disease. Survival time averaged 18.4 months (a range of five to 60 months) for the partial responders, 12.6 months (a range of two to 40 months) for patients with stabilization and seven months (a range of one to 17 months) for those with progression of the disease.

Adult↗

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

Interferon therapy of metastatic renal cell cancer.

There is no curative therapy for metastatic or recurrent renal cell carcinoma (RCC). Almost three-quarters of such patients die of their malignancy in 1 year and less than 5% of such patients are alive at 3 years. Few patients respond to hormonal therapy or chemotherapy, and when responses occur, they are usually brief and partial with little impact on survival. Interferon therapy in metastatic RCC has been associated with response rates of approximately 15-20%, and tumor regression has been demonstrated in patients treated with both partially purified and, more recently, recombinant interferon. Analysis of published trials shows no clear dose-response relationship; however, the highest therapeutic index appears associated with a daily dosage of 5-10 million units. The time to response is variable and may occasionally be prolonged; however, some patients have durations of response exceeding 12 months. Although nephrectomy may be associated with higher response rates, review of available data indicates that nephrectomy has frequently been an eligibility criteria, and indeed there are adequate descriptions of responses in patients that have not undergone this procedure. Patients with pulmonary metastases have the highest response rate. Recently, laboratory and clinical investigations of interferons and several chemotherapeutic agents, notably vinblastine, suggest synergy, but further data is needed to confirm these findings. The role of interferon therapy in improving survival is unknown. There is little doubt, however, that symptomatic patients who respond to interferon therapy may show improvement in their quality of life and prolongation of survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

Fatal esorubicin-induced cardiomyopathy: report of a case and review of the literature.

A case of fatal dilated cardiomyopathy induced by esorubicin (ESO) at a total dose of 740 mg/m2, given in 27 doses over 650 days, is reported. The sudden onset, rapid clinical deterioration, and fatal outcome are detailed. The outcome was not predicted by serial rest ejection fractions or clinical signs. The data from animal studies, phase 1 and phase 2 clinical testing, are reviewed, demonstrating the almost complete absence of reports of ESO-induced cardiotoxicity. Studies reviewing ejection fractions and myocardial biopsy scores show that ESO can be cardiotoxic and may produce fatal dilated cardiomyopathy.

Cardiomyopathies↗

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↗

PubMed1988

Follow-up after stage II breast cancer: a comparative study of relapsed versus nonrelapsed patients.

A retrospective study was undertaken to compare the frequency of scheduled and unscheduled (extra) visits and the signs and symptoms reported on such visits for 31 patients with relapse and 31 matched relapse-free patients all of whom had completed adjuvant treatment for stage II breast cancer. All patients had been treated with the same identical adjuvant therapy program and all had the same regular follow-up schedule, including clinic visits for history and physical examination every 6 months and chest x-ray, complete blood profile, bone scan, and mammogram yearly. Almost all (29/31) relapsed patients had signs or symptoms as the first indicator of recurrence. During a follow-up period of 13-16 months, the relapsed and nonrelapsed patients had a total of 89 and 81 visits, respectively, with an unscheduled visit occurring for almost every two routine visits. Almost all of the 89 total visits for relapsed patients and almost 75% for nonrelapsed patients were associated with signs or symptoms, a majority of which could have been due to cancer recurrence. We conclude that history and physical examination generally provide the first clues to recurrence but that such symptoms and signs are frequently reported by nonrelapsed patients as well as those with recurrence.

Antineoplastic Combined Chemotherapy Protocols↗

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↗