Carcinoma of the prostate gland is one of the most common malignancies in males. This study was undertaken to determine which factors predict the course and outcome of patients treated with first ...line hormonal manipulation. A total of 144 patients with Stage D2 prostate cancer who received androgen deprivation therapy were studied. Pretreatment parameters analyzed were age, performance status, analgesia usage, concurrent disease, histologic differentiation, hemoglobin, leukocyte and platelet count, serum creatinine, alkaline phosphatase, lactate dehydrogenase, prostate specific antigen, total and prostatic acid phosphatase, serum testosterone, follicle stimulating and luteinizing hormone levels, number of metastatic sites and bone scan grade. Only initial serum testosterone (> 10 nmol/l) had a positive impact on response (p = 0.0304), whereas age older than 60 years had a positive impact on time to progression (16 vs. 11 months, p = 0.0414). Both serum testosterone (26 vs. 20 months, p = 0.003), and age (28 vs. 17 months, p = 0.036) had a significant influence on overall survival. Low testosterone, indicating androgen independence, and a younger age, seem to result in a more aggressive disease and a poorer prognosis in advanced prostate cancer.
Background: We report the first results of a randomized trial assessing a new oral aminobisphosphonate, ibandronate, in patients with bone metastases from breast cancer. Patients and methods: ...Patients (n = 435) received placebo, or oral ibandronate 20 mg or 50 mg once-daily for 96 weeks. The primary efficacy measure was the number of 12-week periods with new bone complications skeletal morbidity period rate (SMPR). Multivariate Poisson regression analysis assessed the relative risk reduction of skeletal-related events. Secondary efficacy analyses included bone pain and analgesic use. Adverse events were monitored. Results: SMPR was significantly reduced with oral ibandronate placebo 1.2, 20 mg group 0.97 (P = 0.024), 50 mg group 0.98 (P = 0.037). Ibandronate 50 mg significantly reduced the need for radiotherapy (P = 0.005 versus placebo). The relative risk of skeletal events was reduced by 38% (20 mg dose) and 39% (50 mg dose) versus placebo (P = 0.009 and P = 0.005). The tolerability profile of ibandronate was similar to placebo. Conclusions: Oral ibandronate is an effective and well-tolerated treatment for metastatic bone disease. The 50 mg dose is being further evaluated in clinical trials, and this dose was recently approved in the European Union for the prevention of skeletal events in patients with breast cancer and bone metastases.
Breast cancer heterogeneity dictates lengthy follow-up to assess outcomes. Efficacy differences for three regimens that are based on adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) ...are presented in this article, but cancer recurrence sites, time of relapse, subsequent primary cancers, and causes of death in the natural history of node-positive breast cancer are emphasized.
Beginning in 1975, 905 patients with node-positive cancer were randomly assigned to receive CMF or two regimens of CMF plus other agents. Median follow-up is 22.6 years. The natural-history analysis was performed on a subset of 814 patients.
Eighty percent of the 599 women known to have died, died of metastatic breast cancer. Only 8.5% of the deceased women died of a cause other than breast cancer, a second or third cancer, or adjuvant chemotherapy toxicity. One hundred five women (12.8%) developed other primary cancers, with 49 (46.6%) occurring in the contralateral breast. Therapeutic efficacy differences of the CMF regimens reported earlier have been maintained more than 20 years later. For certain subsets, the five-drug regimen had advantages over CMF. Bone was the most common recurrence site. The longest interval to relapse has been 23.5 years, and 18% of those who relapsed did so more than 10 years later.
Despite adjuvant chemotherapy, a large majority (80%) of women with node-positive breast cancer die of the disease, and many recurrences develop more than 10 years later. CMF plus vincristine and prednisone provides a benefit compared with CMF, but the magnitude varies with the number of involved nodes. Outcome trends in earlier analyses of this study were maintained even years later.
A randomized trial was performed in premenopausal postoperative women with ipsilateral axillary node-positive (N+) breast carcinoma and known estrogen receptor (ER) status to assess the efficacy of ...an Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH)-based induction regimen and 5 or more years of tamoxifen (Tam).
Patients received 12 28-day cycles of cyclophosphamide 100 mg/m2 orally days 1 to 14, methotrexate 40 mg/m2 intravenously (IV) days 1 and 8, fluorouracil 600 mg/m2 IV days 1 and 8, prednisone 40 mg/m2 orally days 1 to 14, and Tam 10 mg orally twice daily (CMFPT), or the same regimen plus halotestin 10 mg orally twice daily (CMFPTH) alternating monthly with 22-day cycles of vinblastine 4.5 mg/m2 IV day 1, Adriamycin 45 mg/m2 IV day 1, thiotepa 12 mg/m2 IV day 1, halotestin, and Tam (ALTER). Prednisone in the ALTER regimen was stopped after the second CMFPTH cycle. After 12 cycles, patients were again randomized to stop or continue Tam. After 5 years, patients on Tam were again randomized to continue or stop Tam; the results from this randomization are still coded. Among 533 analyzed induction cases, 263 received CMFPT and 270 ALTER. Among 396 analyzed maintenance cases, 201 continued Tam and 195 were observed. Pretreatment characteristics were balanced among treatments. The median follow-up times are 5.1 years for induction and 4.1 years for maintenance.
The time to relapse (TTR) was superior for the ALTER regimen (P = .04) and for the maintenance Tam (P = .05). Overall survival comparisons between the regimens are not statistically different. A longer TTR was associated with decreasing nodal involvement, ER+ status, and increasing age. The favorable effects of decreasing nodal involvement and ER+ status carried over to survival; a progesterone receptor-positive (PgR+) status and decreasing tumor size were also associated with longer survival. Development of amenorrhea was associated with improved TTR and survival. Toxicity was similar for the two induction regimens and for the two maintenance regimens. Overall relapse patterns were similar among the induction regimens, but continuing Tam led to fewer locoregional relapses.
The results suggest significant overall TTR therapeutic benefits of an Adriamycin-containing alternating induction regimen and of continuing maintenance Tam therapy for at least 5 years.
Sixteen patients with histologically confirmed inoperable hepatocellular carcinoma were treated with vindesine 3 mg/m2 i.v. weekly. Anemia, leukopenia and neuritis were documented but no severe or ...life-threatening toxicity was seen. There were no objective responses among the 14 evaluable patients. Eight had a no change status (median duration of 16 weeks, range 6-33), while the remaining 6 had progressive disease as their best evaluation. The median survival time was 20 weeks. Vindesine does not have a therapeutic effect in patients with advanced hepatocellular carcinoma.
During the past year, little of finite value has been published to change the approach to combined treatment modalities for the patient with gastrointestinal cancer. The value of adding other ...modalities to surgery to improve the cure rate has been marginal. Neoadjuvant and adjuvant treatment appear to be making inroads into the treatment of esophagus cancer, and newer development of less toxic treatment offers promise for the future. In stomach cancer, combined modality treatment is only of value for patients with locally advanced disease. In the United States, adjuvant chemotherapy is accepted as being of value for patients with colon cancer, and adjuvant treatment with both radiotherapy and chemotherapy is considered to be best for patients with surgically treatable rectum cancer. Primary liver cancer continues to offer a challenge for combined modality treatment, but a call for prospective, randomized control trials seems to be in order.
A randomized comparison of the relative efficacy and toxicity of daunorubicin (DNR) at 30 or 45 mg/sq m or adriamycin (ADM) at 30 mg/sq m, given on the first 3 days of a 7-day continuous infusion of ...cytosine arabinoside (ara-C) at 100 mg/sq m/day. shows the outcome to be dependent on anthracycline, dose, and patient age. DNR 45 is significantly better than DNR 30 or ADM 30 for inducing complete remissions (CR) in patients younger than 60 yr, (72%. 59%. 58% CRs. respectively). DNR 30 is better than DNR 45 or ADM 30 for inducing CR in patients older than 60 yr (47%, 31 %, 35%. respectively). There was a corresponding shift in the induction mortality for the age. dose, and anthracycline groups. Adriamycin was significantly more toxic to the gastrointestinal tract than daunorubicin. The duration of complete remission, with cyclic courses of maintenance therapy, was independent of the patient's age. the dose, or choice of anthracycline used in induction, and of whether the maintenance courses were given every 4 wk or every 8 wk.
Seventy-six women with previously treated breast cancer were randomized to receive mitomycin (M) or M plus high-dose oral medroxyprogesterone acetate (MMPA). Patients were balanced with respect to ...age, performance status, hormone receptor status, previous treatment, and number of metastatic sites. There were more patients with visceral metastases in the M arm of the study. Side effects were tolerable and not significantly different for the two regimens. No life-threatening toxicity occurred. Objective response was documented in 4 of 37 patients on M and 11 of 39 on MMPA. On M the median time to treatment failure (TTF) was 3 months, and median survival was 7.8 months. On MMPA the median TTF was 4.4 months, and median survival was 9.7 months. There was a tendency for higher response and longer TTF and survival on MMPA, but statistical significance was not reached (p = 0.09).
Ninety-seven eligible and evaluable women with metastatic breast cancer were placed on a prospective clinical protocol to evaluate the use of continuous cyclic therapy with dibromodulcitol, ...doxorubicin, vincristine, tamoxifen, and fluoxymesterone (DAVTH) v DAVTH alternating with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP); and the use of pretreatment and serial carcinoembryonic antigen (CEA) levels in these patients. Continuous DAVTH and DAVTH/CMFP were equivalent therapies with respect to response rates, time to treatment failure (TTF), and survival. Pretreatment CEA levels were elevated (greater than 5 ng/mL) in 42/97 patients and less than 5 ng/mL in the remaining patients. Patients with elevated pretreatment CEA levels were more likely to be estrogen receptor (ER) positive (P = .006), to have prolonged disease-free intervals (P = .017), to have hepatic (P = .004) and/or osseous (P = .01) metastases, and to have multiple sites of metastatic disease (P = .004). Pretreatment CEA levels did not significantly predict for overall response rates, TTF, or survival; nonetheless, those patients with low pretreatment CEA levels had more complete responses (CRs) (16/55 v 4/42; P = .02). Serial CEA levels during therapy revealed a number of interesting patterns. During the first 4 months of treatment, serial CEA levels in responding patients either (1) progressively declined (15/29 women with elevated pretreatment CEA levels), or (2) initially rose significantly (mean, 243% of pretreatment value) and then declined (14/29 women with elevated pretreatment CEA levels). Peak CEA levels in the latter patients were seen 27 to 135 days following initiation of cytotoxic therapy. In some patients the initial increase in the CEA level was incorrectly interpreted as evidence of impending disease progression. CEA levels frequently increased around the time of clinical disease progression. However, rising CEA levels rarely provided a clinically meaningful lead time before the appearance of other clinical evidence of disease progression. These data suggest that routine pretreatment and monthly serial CEA levels in metastatic breast cancer patients have minimal use in clinical practice. Two further noteworthy findings were observed in this prospective study. First, patients with an unknown ER status had a prolonged median survival when compared with patients with ER positive or negative tumors; this appeared to be related to prolonged disease-free intervals in ER unknown patients. Second, two case of secondary acute leukemia were seen in patients treated with continuous DAVTH therapy.
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