Docetaxel versus docetaxel alternating with gemcitabine as treatments of advanced breast cancer: final analysis of a randomised trial.

BACKGROUND: Alternating administration of docetaxel and gemcitabine might result in improved time-to-treatment failure (TTF) and fewer adverse events compared with single-agent docetaxel as treatment of advanced breast cancer. PATIENTS AND METHODS: Women diagnosed with advanced breast cancer were randomly allocated to receive 3-weekly docetaxel (group D) or 3-weekly docetaxel alternating with 3-weekly gemcitabine (group D/G) until treatment failure as first-line chemotherapy. The primary end point was TTF. RESULTS: Two hundred and thirty-seven subjects were assigned to treatment (group D, 115; group D/G, 122). The median TTF was 5.6 and 6.2 months in groups D and D/G, respectively (hazard ratio 0.85, 95% confidence interval 0.63-1.16; P = 0.31). There was no significant difference in time-to-disease progression, survival, and response rate between the groups. When adverse events were evaluated for the worst toxicity encountered during treatment, there was little difference between the groups, but when they were assessed per cycle, alternating treatment was associated with fewer severe (grade 3 or 4) adverse effects (P = 0.013), and the difference was highly significant for cycles when gemcitabine was administered in group D/G (P < 0.001). CONCLUSION: The alternating regimen was associated with a similar TTF as single-agent docetaxel but with fewer adverse effects during gemcitabine cycles.

Intensity of diagnostic and treatment activities during the end of life of patients with advanced breast cancer.

The aim of this study was to assess the intensity of diagnostic testing and cancer treatment of 335 women with advanced breast cancer during their last 6 months before death between 1995 and 1998 in the Pirkanmaa and Satakunta health care districts and to compare it to the practice in earlier decades, the 1970s and 1980s. Data for 1990s material were collected from medical records in 30-day periods starting from the patient's death backwards. In this material 46.9% of all laboratory tests and 40% of radiological tests during the last 6 months of life were made during the last 2 months prior to death. In the last month 63.9% of patients continued on endocrine therapy and 19.7% on chemotherapy. Patient symptoms and deterioration in general condition showed the appropriate point to discontinue cancer-related treatment and concentrate on palliation of symptoms to be about 2 months prior to death. Resources devoted to diagnostic investigations and treatment of cancer in terminally ill patients could be better used for their care. This would be more likely to improve patients' quality of life and save resources.

Epirubicin/docetaxel regimen in progressive breast cancer-a phase II study.

The purpose of this investigation was to evaluate the efficacy and toxicity of 6 months' treatment with the combination of epirubicin and docetaxel in metastatic breast cancer. Thirty-eight women (mean age 51 years, range 35-72) with metastatic breast cancer were treated with a regimen of epirubicin 75 mg/m and docetaxel 75 mg/m every 3 weeks, given 4 times if progression was seen upon evaluation after 4 courses or 8 times in responding/stable patients. The patients received 285 cycles of combination treatment and two treatments with docetaxel or epirubicin alone. When neutropenia with fever was observed, further cycles were given with dose reduction. The median cumulative docetaxel dose was 462 mg/m (range 199-600) and that of epirubicin 476 mg/m (range 199-740). The overall response rate was 54% (95% CI 37-71), with a median duration of response of 14.8 months (95% CI 8.8-27.8). Median time to progression was 12 months, median survival 26 months. Neutropenia below 0.5 x 10 /l occurred following 113 (39%) of the total of 285 cycles given; 21 patients (55%) were hospitalized for febrile neutropenia. We conclude that dose tailoring is required in treatment with an epirubicin and docetaxel regimen to avoid grade 3/4 adverse effects in a significant number of patients treated for metastatic breast cancer.

Delayed diagnosis and large size of breast cancer after a false negative mammogram.

The aim of this prospective, multicentre study was to investigate the effects of a false negative mammogram on treatment delay and tumour size. Among 306 consecutive women with histologically diagnosed, invasive breast cancer, the frequency of a false negative mammogram was small (13%) among women aged over 50 years, but 35% among those aged 50 or younger (P < 0.0001). Forty-five per cent of the women with a false negative mammogram had a longer than 2-month and 29% a longer than 6-month interval from mammography to surgery as compared with only 2 and 0% of women, respectively, who had a true positive mammogram (P < 0.0001 for both). Women with a false negative mammogram and a longer than 2-month interval to surgery had larger primary tumour size (60 versus 26% pT2-4, P = 0.005) and more often positive axillary nodes (60% versus 32% pN+, P = 0.03) at the time of surgery than those with a shorter delay. We conclude that a false negative mammogram is common in women younger than 50, and may lead to treatment delay and advanced clinical stage.

A flow cytometric analysis of 23 carcinoid tumors.

Twenty-three carcinoid tumors were investigated from paraffin-embedded tissue with flow cytometry (FCM) in order to correlate the DNA ploidy with clinical variables. DNA aneuploidy was found in ten tumors (45%) and one tumor was classified as tetraploid. Diurnal urinary excretion of 5-hydroxy indolic acetic acid (5-HIAA) was known to be elevated in seven of eight diploid tumors and in four of seven aneuploid carcinoids with distant metastases. Six (55%) of the diploid tumors had not given rise to metastases at the time of diagnosis, compared with three (30%) of the aneuploid tumors. Six of seven patients with an aneuploid tumor and three of five patients with a diploid tumor, observed for at least 10 years, died of the disease. It was concluded that, unlike in earlier studies with static DNA cytometry, DNA aneuploidy is common in human carcinoid tumors and may occur in tumors secreting biogenic amines.

Serum creatine kinase and lactate dehydrogenase during cardiac irradiation.

Thirty patients irradiated to a major part of the heart had serial determinations of serum total creatine kinase (S-CK), creatine kinase subunit B (S-CK-B), total lactate dehydrogenase (S-LD) and lactate dehydrogenase isoenzyme 1 (S-LD-1) activity at the beginning, at the end and 1-4 months after radiotherapy. One patient had an elevated total S-CK activity three months after radiotherapy, but none of the patients had an elevated S-CK-B activity during follow-up. Three patients had elevated serum LD before irradiation, two patients during and two patients after radiotherapy, but only one patient had an elevated S-LD-1 activity, which decreased during irradiation. We conclude that the heart muscle is not injured by cardiac irradiation to such an extent that CK, CK-B, LD and LD-1 activities rise in serum, if moderate doses (39-62 Gy, NSD 1,137-1,775 rets) are delivered to the heart.

Combination chemotherapy with dacarbazine and lomustine in disseminated malignant melanoma.

Thirty-eight patients with disseminated malignant melanoma (stage IV) who had not received previous chemotherapy were given lomustine 50 to 80 mg/m2 orally on day 1 and dacarbazine 400 mg intravenously on days 1 to 3 with intervals of 6 weeks. Three of the 36 evaluable patients showed complete response (8%), 4 partial response (11%), and 5 had stable disease for at least 3 months (13%). The responding patients had metastases confined to cutaneous, nodal or pulmonary sites. None of the patients with liver, osseous or cerebral metastases, or patients with Karnofsky's status of less than 80, responded. Patients with more than two years from the diagnosis to the start of the chemotherapy were more likely to achieve objective response (p less than 0.05). Eighty-four per cent of the patients had nausea or vomiting, but otherwise toxicity was minimal.