Ritva Valavaara

Safety and Efficacy Results of a Randomized Trial Comparing Adjuvant Toremifene and Tamoxifen in Postmenopausal Patients With Node-Positive Breast Cancer

PURPOSE In this multicenter trial, toremifene 40 mg/d was compared with tamoxifen 20 mg/d, both given orally for 3 years to postmenopausal, axillary node-positive women after breast surgery. PATIENTS AND METHODS The first 899 patients (toremifene, n = 459; tamoxifen, n = 440) of the total of 1,480 patients accrued to the trial were included in this scheduled safety analysis. The mean follow-up time was 3.4 years. RESULTS The two treatment groups were well balanced with respect to patient and disease characteristics. The subjective side-effect profile was similar in both treatment groups. Slightly more vascular complications (deep vein thromboses, cerebrovascular events, and pulmonary embolisms) were seen among tamoxifen-treated patients (5.9%) as compared with toremifene-treated patients (3.5%) (P: =.11), whereas bone fractures (P: =.09) and vaginal leukorrhea (P: =.05) were more common in the toremifene group. The number of subsequent second cancers was similar. The breast cancer recurrence rate was 23.1% (n = 106) in the toremifene group and 26.1% (n = 115) in the tamoxifen group (P: =.31). When only patients with estrogen receptor (ER)-positive cancer were considered (n = 556), the risk for breast cancer recurrence was nonsignificantly lower among the toremifene-treated women, with a hazards ratio of 0.74 (90% confidence interval, 0.52 to 1.04; P: =.14). The mean time to breast cancer recurrence and overall survival were similar in both groups. CONCLUSION The side-effect profile of toremifene resembles that of tamoxifen. The efficacy of toremifene seems to be no less than that of tamoxifen. The trend for fewer breast cancer recurrences in the ER-positive subgroup is encouraging, but a longer follow-up is needed to confirm this.

Serum lipid levels during and after adjuvant toremifene or tamoxifen therapy for breast cancer

Tamoxifen decreases serum cholesterol (S-cholesterol) level about 10% and low-density lipoprotein cholesterol (S-LDL) 15–20%, but in most studies it has increased serum triglyceride levels and had little effect on serum high-density cholesterol (S-HDL). The effect of another antiestrogen, toremifene, on the serum lipid profile has not been completely studied. We monitored serum lipid levels longitudinally in 141 axillary node-positive postmenopausal breast cancer patients who received randomly either 40 mg toremifene or 20 mg tamoxifen as adjuvant therapy for 36 months, and in 34 postmenopausal women who received no adjuvant systemic therapy after surgery for axillary node-negative breast cancer. No significant differences were found between the drugs in their effects on S-cholesterol, LDL, HDL, or triglyceride levels, or on the cholesterol-to-HDL or LDL-to-HDL ratios. For both drugs the S-cholesterol and S-LDL absolute lowering effect was the greater the higher the pretreatment level. For a patient with a median pretreatment value, toremifene decreased S-cholesterol 6% and tamoxifen 13%, and S-LDL decreased by 13% and 23%, respectively, at 6 months of therapy. Six months after stopping three-year antiestrogen therapy S- cholesterol and S-LDL levels had returned to the pretreatment levels. In conclusion, we found no major differences between 40 mg toremifene and 20 mg of tamoxifen in their effect on the serum lipid levels, which return to the pretreatment levels within 6 months after cessation of therapy.

High dose toremifene in advanced breast cancer resistant to or relapsed during tamoxifen treatment

SummaryFifty patients with advanced breast cancer refractory to prior tamoxifen therapy were assigned to investigational treatment with high-dose toremifene administered 120 mg orally twice a day. Treatment was generally well tolerated. The majority (80%) of the patients had no side effects, and among the remaining 10 patients reported side effects were mostly mild and/or transient. Two objective tumor responses were observed: one complete response (CR), duration 6.2 months, and one partial response (PR), duration 8 months. The response rate was thus 4% (95% CI: 0.5 to 14%). In addition 3 patients experienced a mixed response, some metastatic sites responding, while at other sites disease progressed; 22 patients had disease stabilization for > 2 months. A subset analysis disclosed that a small subgroup of patients, including 7 patients in this study, who had achieved CR at some of the sites during preceding tamoxifen therapy, experienced a long progressionfree time during high dose toremifene treatment. The median time to progression in this subgroup of patients was 9.4 months (95% CI: 3.8 to 9.4) as opposed to 2.1 months (95% CI: 2.0 to 2.8) for all the remaining 43 patients, which is a significant decrease in disease progression (p < 0.03). Such results reveal that although this kind of second-line hormonal treatment with high dose toremifene cannot be recommended for all tamoxifen failures, there might be a subset of patients, i.e. those who achieve CR in some lesion during tamoxifen therapy, who benefit from this type of treatment.

High dose toremifene (240 mg daily) is effective as first line hormonal treatment in advanced breast cancer an ongoing phase II multicenter Finnish-Latvian cooperative study

SummaryThe efficacy of high dose toremifene (240 mg daily) in postmenopausal women with advanced breast cancer is investigated in this ongoing study. At present, 38 patients are fully evaluable. Ten patients have CR (26%), 16 PR (42%) (objective response rate 68%), 8 NC (21%), and 4 PD (11%). Most objective responses are in soft tissue tumors (14/17, 82%). The response rate is equally high in patients with positive or unknown estrogen receptor (ER) status. Median duration of responses and survival are not yet evaluable. Of 48 patients evaluable for side-effects, 22 (46%) experienced some kind of toxicity, which was mild in 64% of cases, moderate in 29%, and mostly of estrogenic type. The study will continue to confirm the results thus far obtained.

Phase II trials with toremifene in advanced breast cancer: A review

SummaryThe antitumor activity of the new triphenylethylene drug toremifene has been studied in advanced breast cancer of postmenopausal women as first line treatment at dose levels of 20, 60, and 240 mg, and as second line or later treatment at high dose levels of 200–240 mg. The response rates (complete + partial response) have been 21% with 20 mg (14 patients), 52% with 60 mg (93 patients in three separate trials), and 68% with 240 mg (38 patients) as first line treatment. After failure on previous therapy (hormonal or chemotherapy) the response rates have been about 10% with 200 mg of toremifene (71 patients in two different trials). In patients whose disease had previously responded to tamoxifen with at least stabilization, the response rate with toremifene has been 23%; but among unselected patients, including patients progressing during adjuvant tamoxifen, the response rate (CR + PR) with toremifene in tamoxifen failures has been 3%. If long lasting (more than 5 months) stabilization of the disease is also considered, a further 20% of previously treated patients have benefitted from toremifene. The treatment has been well tolerated at all dose levels. The most reported side effects have been hot flushes (8–19%) and nausea (8%). 0–6% of patients in different trials have interrupted the treatment because of side effects

Treatment Results of Nasopharyngeal Cancer a nationwide survey from Finland

The nationwide experience of treating nasopharyngeal cancer in Finland during the period 1980-1989 was reviewed. Of the 107 patients included in the present analysis, 13 were treated palliatively only, and three had metastatic disease at their first clinical presentation, whereas the rest (n = 91) were treated with radical radiotherapy, of whom, 8 patients received adjuvant chemotherapy after radiotherapy. The 5-year actuarial survival rates of these 91 patients was 52%, and by the UICC stage they were classified as follows: stage I 75% (n = 12), stage II 60% (n = 5), stage III 59% (n = 34), and stage IV 38% (n = 40). According to the Coxs stepwise proportional hazard model the most important factors influencing favourable survival were the total dose of radiotherapy expressed in terms of Biologically Effective Dose (BED) with a time factor, a small size of the primary tumour and a high performance status according to the WHO scale, whereas the most important factors influencing the local control analysis were the total dose of radiotherapy (expressed in BED) and the cervical lymph node status.

Neodymium YAG Contact Laser in the Treatment of Cancer of the Mobile Tongue

The aim of this study was to evaluate the usefulness of a contact neodymium YAG laser for the treatment of squamous cell carcinoma (SCC) of the mobile tongue in 35 patients. The TNM stage and histologic grade were as follows: T1, n = 20; T2, n = 11; T3, n = 4; and N0, n = 33; N1, n = 2; G1, n = 20; G2, n = 10; and G3, n = 5. The surgical treatment consisted of a hemiglossectomy or resection with adequate margins in 28 cases, and an ipsilateral neck dissection was also performed in 7 patients. Radiotherapy to a mean tumor dose of 62-64 Gy and an elective dose of 50 Gy to the cervical lymph nodes was given to 14 patients. The radiotherapy was preoperative in 12 patients and postoperative in 2. Tongue resection was easily performed using the contact neodymium YAG laser, with a mean operation time of 31 min and intraoperative bleeding varying from negligible to 100 cm 3 . During postoperative follow-up no major complications occurred: cases with minor hemorrhage were easily controlled on the ward and 1 patient had a bleed on the 14th postoperative day necessitating hospitalization. The resection was histologically radical in all cases. During follow-up one patient had a local recurrence (T2N0, G3) and four failed in the neck (T1N0 G2, T1N0 G2, T1N0 G2, T2N0 G2), three of whom were successfully salvaged with a neck dissection and radiotherapy. One patient with osteoradionecrosis was diagnosed and treated curatively. Two patients died of their tongue cancer (T2N0 G3, T2N0 G2), 1 died from a second primary tumor (T2N0 G1) and 2 of intercurrent disease with no evidence of cancer; 30 patients (86%) are still alive with no evidence of disease. The function of the tongue in all patients in this sample was good to satisfactory. The major complaint was xerostomia in the irradiated patients. In conclusion, the contact neodymium YAG laser appears to be suitable for resection of T1-T2 SCCs of the oral tongue. In this limited patient sample T stage or grade did not predict failures in the neck. Biologic predictive markers need to be evaluated.

Results of Cystectomy with and Without Preoperative Radiotherapy in Carcinoma of the Urinary Bladder

During a period of 13 years, 84 patients underwent total cystectomy for transitional cell carcinoma of the bladder. The corrected 5-year survival rate was 58%. The operative mortality was 5 patients (6%). The 5-year survival rate of 42 patients who were treated by surgery alone was 53%, whereas that of 42 patients who received preoperative radiation of 30-40 Gy was 65%. The prognoses of the patients were dependent on the histological differentiation and the extent of the primary tumour within each treatment group.