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Biomedical subjects

H B Muss

Publications and source records attributed to H B Muss.

At least 109 records · Page 6Linked to original sources

A randomized multicenter trial comparing mitoxantrone, cyclophosphamide, and fluorouracil with doxorubicin, cyclophosphamide, and fluorouracil in the therapy of metastatic breast carcinoma.

Three hundred thirty-one women with metastatic breast cancer were randomized to receive combination chemotherapy with either cyclophosphamide, Novantrone (mitoxantrone; Lederle Laboratories, Wayne, NJ), and fluorouracil (CNF) or cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and fluorouracil (CAF). Patients could not have had prior chemotherapy, although adjuvant chemotherapy was acceptable. Initial doses were 500 mg/m2 of cyclophosphamide and 500 mg/m2 of fluorouracil with either 10 mg/m2 of mitoxantrone or 50 mg/m2 of doxorubicin, administered intravenously (IV) on day 1 and repeated every 3 weeks. There were no statistically significant differences in pretreatment or prior therapy characteristics between the groups. For patients assigned to the CNF and CAF groups, respectively, 25 (18%) were premenopausal, 39 (40%) were estrogen receptor (ER) negative, 39 (38%) had a disease-free interval less than 1 year, and 24 (26%) had received prior adjuvant chemotherapy. All patients were compared for response rate, duration of response, time to progression or death, time to treatment failure (TTF), and survival. None of these parameters were statistically significant favoring one regimen over the other. The response rate (complete [CR] and partial response [PR]) was 29% for the CNF group (95% confidence interval of 22% to 37%) and 37% for the CAF group (95% confidence interval of 29% to 45%). The median response duration and TTF were 171 days and 125 days for the CNF group and 254 days and 147 days for the CAF group, respectively. The median survival times for the CNF group and the CAF group were 377 and 385 days, respectively. The major dose-limiting toxicity for both regimens was leukopenia, manifested as granulocytopenia. The incidence of stomatitis/mucositis was 10% in the CNF group and 19% in the CAF group. Alopecia occurred in 49% of CNF patients (severely for 4%) and in 86% of CAF patients (severely for 39%). Nausea/vomiting occurred in 80% of CNF patients and in 81% of CAF patients; the degree of severity was also comparable. There was significantly less cardiotoxicity observed in the CNF group compared with the CAF group. Although CNF is somewhat less effective in overall response rate, survival curves are identical. CNF can be offered to patients who reject anthracycline-containing regimens because of fear of alopecia.

Adult↗

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↗

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↗

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↗

Cellular blue nevus simulating metastatic melanoma: report of an unusually large lesion associated with nevus-cell aggregates in regional lymph nodes.

A young Caucasian woman had a large area of blue-gray discoloration on the flank and palpable axillary lymph nodes. The discolored area had enlarged during a recent pregnancy, contained multiple subcutaneous nodules, demonstrated increased cellularity and mitotic activity, and was associated with an axillary lymph node containing black streaks within the capsule. Although the lesion was initially considered to be a metastatic malignant melanoma, re-evaluation showed it to be a benign cellular blue nevus with benign nevus-cell aggregates within a regional lymph node. We report this case to emphasize how cellular blue nevus can simulate malignant melanoma and to increase physician awareness of this benign variant of melanocytic nevus so that inappropriate surgery and chemotherapy can be avoided.

Adult↗

Mitoxantrone in the treatment of advanced non-squamous carcinoma of the cervix (a phase II trial of the gynecologic oncology group).

Twenty-five evaluable patients with advanced non-squamous carcinoma of the uterine cervix were treated with mitoxantrone 12 mg/m2 every three weeks. All patients had good performance status and measurable disease and only 11 had received prior chemotherapy. One complete and one partial response were noted among 15 patients with no prior chemotherapy while no responses were seen in 11 previously treated patients. The major toxicity was myelosuppression; other toxicity was mild. The median progression-free interval was 2.1 months and median survival 4.3 months. Mitoxantrone displays minimal activity in patients with advanced non-squamous carcinoma of the cervix.

Adenocarcinoma↗

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↗

Neoadjuvant therapy for advanced squamous cell carcinoma of the cervix: cisplatin followed by radiation therapy--a pilot study of the Gynecologic Oncology Group.

Eleven patients with untreated advanced squamous cell carcinoma of the cervix (FIGO Stage IIIB and IVA, or positive paraaortic nodes) were treated with cisplatin 50 mg/m2 every 3 weeks for six courses prior to irradiation therapy (RT). Six patients completed six courses of cisplatin prior to RT with one complete and two partial responses (PR). Five other patients did not complete cisplatin therapy; two progressed after two and three courses, one had a PR after three courses and refused further therapy, one refused treatment after two courses and one elected to begin RT after one course. Two patients had reversible nephrotoxicity. No other major toxicity was noted. Six patients had stem cell assay prior to treatment and assay results were predictive of cisplatin response in five. Only one patient remains alive at 44+ months. Cisplatin chemotherapy prior to irradiation therapy is feasible and without substantial toxicity but is unlikely to be of benefit in patients with advanced cervical cancer.

Adult↗

Treatment of advanced colorectal carcinoma with actinomycin D, vincristine, methyl-CCNU, and methotrexate.

Twenty patients with advanced colorectal carcinoma were treated with combination chemotherapy consisting of actinomycin D, vincristine, methyl-CCNU, and methotrexate. Fourteen patients had received prior chemotherapy with 5-fluorouracil (5-FU). No complete responses and only one partial response were observed for an overall response rate of 5%. The combination of actinomycin D, vincristine, methyl-CCNU, and methotrexate at the doses and schedule used was of no value in the treatment of patients with metastatic colorectal carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Hematologic monitoring in patients with cancer. A study of the Gynecologic Oncology Group.

A retrospective review of four Gynecologic Oncology Group protocols involving aggressive chemotherapy was carried out to assess the following. Whether granulocyte determinations, which require a differential count resulting in extra cost and time, added pertinent clinical information to that obtained from the white blood cell count alone. If, there is a predictable relationship between the white blood cell count and the platelet count as a reflection of bone marrow toxicity, and whether one can predict when maximum myelosuppression will occur during a treatment program. This data revealed that the white blood count and granulocyte levels are closely related; that rarely is life-threatening thrombocytopenia noted in the absence of leukopenia; and that myelosuppression can occur during any course of treatment and is not predictable. Thus, for these treatment regimens in gynecologic malignancies, the white blood count is sufficient for monitoring toxicity and adjusting future courses of chemotherapy. Only when the white blood count is severely depressed is it necessary to monitor the granulocyte and platelet counts.

Antineoplastic Combined Chemotherapy Protocols↗

Tamoxifen rechallenge: response to tamoxifen following relapse after adjuvant chemohormonal therapy for breast cancer.

Two-hundred seventy-three node-positive primary breast cancer patients with positive estrogen or progesterone receptors were placed on a short-term chemohormonal adjuvant program that included tamoxifen. At present, 64 have relapsed, 19 of whom have been rechallenged with tamoxifen after disease-free intervals (DFI) ranging from 0.4 to 4.4 years. Most patients had only one site of disease recurrence. Two patients have achieved complete remission (CR) and three partial remission (PR) for a CR and PR rate of 26% (95% confidence interval for CR and PR is 9% to 51%). Duration of response has ranged from 3 to 17+ months. Patients who receive short-term adjuvant therapy with tamoxifen and who relapse may respond to tamoxifen rechallenge. In this series, the response rate to tamoxifen rechallenge was similar to the response rate for patients unselected for estrogen receptor status receiving first-line endocrine therapy for breast cancer relapse.

Adult↗

Recombinant alfa interferon in renal cell carcinoma: a randomized trial of two routes of administration.

Ninety-seven patients with recurrent or metastatic renal cell carcinoma were randomized to receive recombinant interferon (IFN) alfa-2b (Intron A; Schering-Plough, Kenilworth, NJ) by either the subcutaneous (SC) or intravenous (IV) route. The SC dosage was 2 X 10(6) IU/m2 three times weekly, and the IV dose 30 X 10(6) IU/m2 for five consecutive days every 3 weeks. Dose escalation to a maximum of 10 X 10(6) IU/m2 SC and 50 X 10(6) IU/m2 IV was allowed for patients with minimal or absent toxicity. Five of 51 of the SC-treated patients (10%) and three of 46 of the IV-treated patients (7%) had a partial response (PR) or complete response (CR). Patients with prior nephrectomy, no prior treatment, and lack of bone metastases were most likely to respond, and a retrospective analysis of this subgroup revealed a 23% response rate. Achievement of response took from 3 weeks to 11 months, while response duration lasted from 3 to 31+ months. All responders had prior nephrectomy; six of eight had no prior chemotherapy or hormonal therapy; five had lung metastases, and none had bone metastases. Regardless of route, almost all patients developed a flu-like syndrome; however, grade 3 or greater toxicity was much more common for IV-treated patients. This trial demonstrates modest, but definite antitumor activity for recombinant interferon in advanced renal cell carcinoma. SC administration with lower dose and toxicity is as effective as treatment administered IV.

Adult↗

Vinblastine infusion in non-Hodgkin's lymphomas: lack of total cross-resistance with vincristine.

Historically, vinblastine given by intravenous bolus injection has not been an effective treatment for non-Hodgkin's lymphomas; vincristine has displayed greater activity. Also, vinblastine has generally been considered to be cross-resistant with vincristine in such patients. In an attempt to overcome these obstacles, a protracted infusion of vinblastine was administered (0.5-1.5 mg/m2 per day for 5 days) and repeated every 3 weeks. Partial responses were observed in 4 of 29 (14%) patients with a variety of non-Hodgkin's lymphoma lasting 2.4, 2.4, 5.5, and 9.0 months. Just prior to treatment the responding patients had received and eventually become refractory to vincristine. These data show a lack of total cross-resistance between vinblastine and vincristine which might have important therapeutic implications in this disease.

Adult↗

Interferon therapy for renal cell carcinoma.

Recurrent or metastatic renal cell carcinoma (RCC) seldom and only briefly responds to hormonal therapy or chemotherapy, with little, if any, impact on overall survival; hence the prognosis is poor. Effects of both partially purified and recombinant interferons have been studied and have yielded response rates of 5% to 27%. In a review of 12 series, the complete and partial response rate was 16% (100 of 632 patients) with a 95% confidence interval of 13% to 19%. Response rates were similar for both partially purified and recombinant interferons. Although no dose-response effect has been clearly demonstrated, daily doses (5 to 10 megaunits) of interferon seem to be associated with the highest therapeutic index. Patient characteristics that suggest potential responsiveness to interferon include minimal or no prior therapy, good performance status, and pulmonary metastases. Although some investigators believe that patients with nephrectomy are more likely to be responsive, a careful review of published literature does not support this. Laboratory observations demonstrating synergistic activity of interferons combined with a variety of chemotherapeutic agents have led to clinical trials for exploring the potential of such treatment. Initial results of combining interferon and vinblastine are encouraging; further studies are under way. Substantial evidence now indicates that interferon is an effective agent in metastatic RCC.

Antibody Formation↗