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Biomedical subjects

C L Vogel

Publications and source records attributed to C L Vogel.

At least 37 records · Page 2Linked to original sources
PubMed1993

Multicenter phase II efficacy trial of toremifene in tamoxifen-refractory patients with advanced breast cancer.

PURPOSE: To explore further the efficacy of high-dose toremifene in patients with advanced breast cancer who had failed to respond to tamoxifen or whose disease had progressed on tamoxifen. PATIENTS AND METHODS: One hundred two perimenopausal or postmenopausal women with metastatic breast cancer refractory to tamoxifen were entered onto a phase II clinical trial of toremifene at a dose of 200 mg/d. The study patients consisted of 28 primarily refractory patients; 43 patients who had relapsed after a prior tamoxifen response; and 31 patients who had relapsed while receiving adjuvant tamoxifen. This was a heavily pretreated group of patients, with 65% having failed chemotherapeutic attempts and 72% having failed two or more hormonal therapies. Forty-nine percent of patients had visceral dominant disease. RESULTS: The objective response rate was 5% (95% confidence interval [CI], 3% to 7%). The median time to treatment failure (TTF) was 10.9 months for the five responders. An additional 23% of patients had stable disease for a median TTF of 7.8 months, whereas the patients who experienced treatment failure had a median TTF of 2.1 months. Whether those patients with stable disease derived clinical benefit or simply had slow progression in an intrinsically indolent disease presentation is uncertain. Common toxicities were generally mild and similar to those encountered with tamoxifen. CONCLUSION: We conclude that there is major cross-resistance between tamoxifen and toremifene and that only occasional tamoxifen-refractory patients will have objective responses to toremifene.

Aged↗
PubMed1992

Survival after first recurrence of breast cancer. The Miami experience.

BACKGROUND: Four hundred thirty-three patients with recurrent breast cancer were treated by the authors at a large medical breast oncology facility from 1976-1982. The median survival time from first relapse (MSFR) for the 193 patients whose survival experience was not confounded by lead-time bias was 26 months. This MSFR is similar to that of most series published in the 1970s and 1980s and is approximately double that of series published in the 1960s. METHODS: In this series, regression analysis identified disease-free interval (DFI), estrogen receptor (ER) status, and dominant disease site as significant prognostic variables, similar to other published series. RESULTS: In 113 patients with known ER values, DFI, and dominant metastatic sites, a prognostic spectrum of MSFR patterns was identified among combinations of these three variables. The MSFR ranged from 15 months for poor risk patients with negative ER values, visceral dominant sites, and DFI of less than 24 months, to more than 90 months for good risk patients with positive ER values, soft tissue dominant sites, and DFI of more than 24 months. Although menopausal status alone was not a significant prognostic variable in regression analysis, 66% of premenopausal patients had a constellation of "poor" prognostic variables. CONCLUSIONS: This type of prognostic factor analysis at first relapse could help identify subsets of patients who might be considered for aggressive investigational therapies such as high-dose chemotherapy with autologous bone marrow reconstitution.

Breast Neoplasms↗
PubMed1992

Postsurgical adjuvant chemotherapy with or without radiotherapy in women with breast cancer and positive axillary nodes: a South-Eastern Cancer Study Group (SEG) Trial.

In a prospective study of 622 women with breast cancer, those with one to three histologically positive axillary lymph nodes were randomised after mastectomy to receive cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2 intravenously on days 1 and 8, and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles (CMF x six), or for twelve cycles of the same chemotherapy (CMF x 12). Those with > or = four positive nodes were randomised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy (RT) followed by six cycles of the same chemotherapy (RT + CMF x six). With about 10 years median follow-up, there was no significant difference in survival or disease-free survival among the three groups. There was evidence of decreased locoregional recurrence in patients with > or = four nodes who received RT + CMF x six (relative risk 0.53, P = 0.067). Multivariate analysis indicated that the presence of > or = four positive nodes (negatively) and the percentage of ideal (full) dose of CMF received (positively) were the strongest factors predictive of survival. This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes. There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with > or = four positive nodes.

Adult↗
PubMed1991

Treatment of metastatic breast cancer.

Relapse of breast cancer connotes a dire prognosis. However, long-term survival with remissions and disease exacerbation are possible using conservative treatment strategies and often sequential hormonal manipulations. Hormonal therapy is the mainstay of metastatic breast cancer treatment for patients with hormonally sensitive tumors; cytotoxic chemotherapy, for patients with hormonally independent tumors. High-dose chemotherapy with autologous bone marrow reinfusion is currently under investigation.

Breast Neoplasms↗
PubMed1991

Dronabinol and prochlorperazine in combination for treatment of cancer chemotherapy-induced nausea and vomiting.

Dronabinol (Marinol, Roxane Laboratories, Columbus, OH) and prochlorperazine were tested alone and in combination in a randomized, double-blind, parallel group, multicenter study. Patients were randomized to receive either 1) dronabinol 10 mg every 6 hr plus placebo; 2) placebo plus prochlorperazine 10 mg every 6 hr; or 3) dronabinol and prochlorperazine, each 10 mg every 6 hr. Antiemetic treatment was begun 24 hr prior to and continued for 24 hr after the last dose of chemotherapy; all was given orally. Only 29% of patients in group 3 versus 47% in group 1 and 60% in group 2 experienced nausea after chemotherapy. In addition, the median duration per episode and severity of nausea were significantly less with combination therapy. Vomiting occurred after chemotherapy in 41%, 55%, and 35% of patients in groups 1, 2, and 3, respectively. The median duration per episode of vomiting was 1 min in group 3 versus two in group 1 and four in group 2. Side effects, primarily CNS, were more common in group 1 than in group 2; addition of prochlorperazine to dronabinol appeared to decrease the frequency of dysphoric effects seen with the latter agent. The combination was significantly more effective than was either single agent in controlling chemotherapy-induced nausea and vomiting.

Adult↗
PubMed1990

A phase I study of 4'-0-tetrahydropyranyladriamycin. Clinical pharmacology and pharmacokinetics.

A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.

Adult↗
PubMed1988

Clinical trial of high-dose oral medroxyprogesterone acetate in the treatment of metastatic breast cancer and review of the literature.

Recent studies have suggested that there are benefits from the use of high-dose parenteral medroxyprogesterone acetate (MPA) in the treatment of metastatic breast cancer. The present study was designed to assess the efficacy and toxicity of high-dose oral MPA in women with clinical parameters suggesting potentially hormonally sensitive metastatic breast cancer. The first 28 patients received 800 mg/day, and 11 of them had received no previous hormone (NPH) therapy. The response rate (complete plus partial) was 63% for those receiving NPH and 12% for those receiving previous hormone (PH) therapy. Toxicity was significant at these doses, especially for women treated for more than 5 weeks. Toxic effects included excessive weight gain, Cushingoid facies, worsening of diabetes mellitus, and other stigmata suggestive of hypercorticism. Nineteen other patients were treated at 400 mg/day with a 60% response rate for 10 NPH patients and 44% for patients with PH treatment. Toxicity was less severe in these patients. The median time to treatment failure was 23 weeks, and to survival, 119 weeks for all treated patients. Moderately high (400 mg/d) and higher dose (800 mg/d) oral MPA are capable of inducing reasonable response rates in patients with NPH treatment. The toxicity of these regimens was significant--profound weight gain was dose limiting in some patients. While effective, high-dose oral MPA is unlikely to supplant tamoxifen as first-line therapy in metastatic breast cancer.

Administration, Oral↗
PubMed1988

Phase II evaluation of teniposide (VM-26) in metastatic breast carcinoma. A Southeastern Cancer Study Group trial.

The Southeastern Cancer Study Group performed a Phase II study of teniposide in previously treated patients with metastatic breast cancer. No responses were observed in 11 evaluable patients who received teniposide 60 mg/m2 by IV infusion for five consecutive days every three weeks. Toxicity was primarily gastrointestinal and hematologic and was frequently severe. This study demonstrated no therapeutic activity for teniposide when given in this dose and schedule to patients with heavily pretreated metastatic breast cancer.

Adult↗
PubMed1988

Phase II trial of recombinant beta (IFN-betaser) interferon in the treatment of metastatic breast cancer.

Nine patients with metastatic breast cancer received 30 x 10(6) I.U. of Interferon - Betaser (Betaseron) intravenously daily times five for two consecutive weeks followed by a two week rest period. Only one patient received more than one such cycle of Betaseron. The drug was well tolerated in eight of these patients. One patient, with liver metastases and liver dysfunction, developed hepatic decompensation during therapy. Toxicity consisted of anorexia, chills, fever, fatigue and nausea with an occasional patient having emesis. One patient developed severe thrombocytopenia, two, significant leukopenia and nine, mild elevations of serum transaminase. Two patients developed beta interferon binding antibodies but none developed neutralizing antibodies. No anti-tumor responses were seen and disease progression occurred rapidly during the four week cycle in eight of nine patients.

Adult↗
PubMed1987

Response to tamoxifen in estrogen receptor-poor metastatic breast cancer.

While hormone receptor values are extremely valuable in breast cancer management, many variables leading to falsely negative receptor results should be considered before clinical decision making in the setting of metastatic disease. At the Papanicolaou Comprehensive Cancer Center in Miami, Florida 271 patients with metastatic breast cancer received tamoxifen over a 4-year period. Only 40 of the 204 patients (19.6%) with available estrogen receptor assay information had pretreatment receptor values classically considered receptor-poor. While four patients had inevaluable tamoxifen trials and 12 patients had "compassionate" use in end-stage situations, 24 patients received tamoxifen therapy in the face of receptor-poor values because of clinical or histopathological correlates suggesting the possibility of false negative assay results. Six of 36 evaluable patients (16.6%), including those treated on "compassionate grounds," responded to tamoxifen, while 6 of 24 more highly selected patients (25%) responded. Response durations in these six patients were 11, 12, 28, 28+, 49, and 51 months, respectively; two of these six also had significant, objective tamoxifen withdrawal responses of 9 and 14 months. Based on these results, it is urged that receptor values are studied and integrated with classical clinical and histopathologic variables before making a clinical decision so that patients with receptor-poor assay results are not prematurely labeled hormonally unresponsive.

Adult↗
PubMed1987

Phase I clinical trial and pharmacokinetics of weekly ICRF-187 (NSC 169780) infusion in patients with solid tumors.

ICRF-187 was given to 62 evaluable patients with advanced solid tumors in a Phase I clinical trial. Weekly infusions were given in dosages ranging from 0.85 g/m2 to 7.42 g/m2 for a total of four weeks with a two week rest period between courses. Dose-limiting hematological toxicity was seen in heavily pretreated patients at a dose of 3.8 g/m2/week. All patients also developed reversible SGOT elevations. In patients with less prior therapy hematologic toxicity was not dose-limiting but hepatotoxicity, manifest by transient SGOT levels greater than 5 times baseline was seen at 7.42 g/m2/week even though only 3/6 patients could receive 4 consecutive weekly doses. At virtually all dose levels tested some patients developed anemia. Other toxicities, including alopecia, nausea, vomiting and reversible serum amylase elevations, were mild. Cumulative monthly doses achieved on this weekly schedule are significantly higher than a 48-hour infusion or daily times 3 or 5 schedule in adults and a daily times 3 schedule in children. Pharmacokinetic studies in eight patients indicate that the drug disappears from the plasma biphasically with a terminal t1/2 of 3.2 +/- 0.9 hr. The total clearance was 288.7 +/- 85.0 ml/hr/kg and the volume of distribution (Vda) was 1.3 +/- 0.4 l/kg. Pharmacokinetics were not dose-dependent from 3.8-7.4 g/m2 and no difference in pharmacokinetics was found in patients studied during the first and second treatments of a course. If Phase II trials of ICRF-187 are to be pursued on this schedule, appropriate doses would be 3.8 g/m2/week X 4 for heavily pretreated and 7.42 g/m2/week for "good risk" patients. Because of erratic hematologic toxicity in heavily pretreated patients, some might only tolerate three weekly doses. In good risk patients transaminitis was significant but reversible, thus, Phase II protocols should include dose escalation schemata.

Adult↗
PubMed1986

Ineffectiveness of levamisole in prolonging remission or survival of women treated with cyclophosphamide, doxorubicin, and 5-fluorouracil for good-risk metastatic breast carcinoma: a Southeastern Cancer Study Group Trial.

A total of 97 women with good-risk metastatic breast cancer received therapy with cyclophosphamide, doxorubicin, and 5-FU; half of these patients were randomly allocated to receive levamisole, 2.5 mg/kg, 2 days of each week in addition to chemotherapy, while the other half received an identical placebo. Good-risk patients consisted of those with bone-only metastasis, or local chest wall recurrence with or without bone metastasis. No significant difference in response rate, duration of disease control, or survival was observed between the groups. No major toxicity was associated with levamisole.

Antineoplastic Combined Chemotherapy Protocols↗