Riikka Huovinen

Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trial.

PURPOSE We report results of a randomized prospective study that compared single agents of low toxicity given both as the first-line and second-line chemotherapy with combination chemotherapy in advanced breast cancer with distant metastases. PATIENTS AND METHODS Patients in the single-agent arm (n = 153) received weekly epirubicin (E) 20 mg/m2 until progression or until the cumulative dose of 1,000 mg/m2, followed by mitomycin (M) 8 mg/m2 every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 500 mg/m2, E 60 mg/m2, and fluorouracil 500 mg/m2 three times per week (CEF) followed by M 8 mg/m2 plus vinblastine (V) 6 mg/m2 every 4 weeks. Exclusion criteria included age greater than 70 years, World Health Organization (WHO) performance status greater than 2, prior chemotherapy for metastatic disease, and presence of liver metastases in patients younger than 50. RESULTS An objective response (complete [CR] or partial [PR]) was obtained in 55%, 48%, 16%, and 7% of patients treated with CEF, E, M, and MV, respectively. A response to CEF tended to last longer than a response to E (median, 12 v 10.5 months; P = .07). Treatment-related toxicity was less in the single-agent arm and quality-of-life (QOL) analysis favored the single-agent arm. No significant difference in time to progression or survival was found between the two arms. Similarly, no difference in survival was found when the patients who received both the planned first-and second-line treatments were compared or when survival was calculated from the beginning of the second-line therapy. CONCLUSION Patients treated with single-agent E followed by single-agent M had similar survival, but less treatment-related toxicity and better QOL as compared with those treated with CEF followed by MV.

Adjuvant Capecitabine, Docetaxel, Cyclophosphamide, and Epirubicin for Early Breast Cancer: Final Analysis of the Randomized FinXX Trial

PURPOSE Capecitabine is an active agent in the treatment of breast cancer. It is not known whether integration of capecitabine into an adjuvant regimen that contains a taxane, an anthracycline, and cyclophosphamide improves outcome in early breast cancer. PATIENTS AND METHODS Women with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive either three cycles of docetaxel and capecitabine (TX) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX; n = 753) or three cycles of docetaxel (T) followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF; n = 747). The primary end point was recurrence-free survival (RFS). RESULTS During a median follow-up time of 59 months, 214 RFS events occurred (local or distant recurrences or deaths; TX/CEX, n = 96; T/CEF, n = 118). RFS was not significantly different between the groups (hazard ratio [HR], 0.79; 95% CI, 0.60 to 1.04; P = .087; 5-year RFS, 86.6% for TX/CEX v 84.1% for T/CEF). Fifty-six patients assigned to TX/CEX died during the follow-up compared with 75 of patients assigned to T/CEF (HR, 0.73; 95% CI, 0.52 to 1.04; P = .080). In exploratory analyses, TX/CEX improved breast cancer-specific survival (HR, 0.64; 95% CI, 0.44 to 0.95; P = .027) and RFS in women with triple-negative disease and in women who had more than three metastatic axillary lymph nodes at the time of diagnosis. We detected little severe late toxicity. CONCLUSION Integration of capecitabine into a regimen that contains docetaxel, epirubicin, and cyclophosphamide did not improve RFS significantly compared with a similar regimen without capecitabine.

Carbon-11-methionine and PET in evaluation of treatment response of breast cancer.

Uptake of L-methyl-11C-methionine (11C-methionine) in breast cancer metastases was studied with positron emission tomography (PET). Eight patients with soft tissue metastases were studied twice: before the onset of chemotherapy (4), hormonal therapy (3) or radiotherapy (1) and 3-14 weeks later. The radioactivity concentration of the low molecular weight fraction of venous plasma samples separated by fast gel filtration was used as input function. The input corrected uptake rate of 11C-methionine (Ki) in breast cancer metastases before the treatment ranged between 0.035 and 0.186 1 min-1 and the standardised uptake value (SUV) between 2.0 and 11.4. The uptake of 11C-methionine into the metastases decreased when clinical objective stability or regression of the metastases was later obtained and increased in cases where progressive disease was seen during treatment. We conclude that metabolic changes in the amino acid metabolism detected by PET precede the clinical response, and may be of clinical value in predicting the treatment response.

Quality of life and physical performance and activity of breast cancer patients after adjuvant treatments

Objective: The study aimed at investigating the quality of life (QoL) and physical performance and activity, and their interrelations, in Finnish female breast cancer patients shortly after adjuvant treatments.

Prospective evaluation of planar bone scintigraphy, SPECT, SPECT/CT, 18F-NaF PET/CT and whole body 1.5T MRI, including DWI, for the detection of bone metastases in high risk breast and prostate cancer patients: SKELETA clinical trial

Purpose. Detection of bone metastases in breast and prostate cancer patients remains a major clinical challenge. The aim of the current trial was to compare the diagnostic accuracy of 99mTc-hydroxymethane diphosphonate (99mTc-HDP) planar bone scintigraphy (BS), 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT and whole body 1.5 Tesla magnetic resonance imaging (MRI), including diffusion weighted imaging, (wbMRI+DWI) for the detection of bone metastases in high risk breast and prostate cancer patients. Material and methods. Twenty-six breast and 27 prostate cancer patients at high risk of bone metastases underwent 99mTc-HDP BS, 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT and wbMRI+DWI. Five independent reviewers interpreted each individual modality without the knowledge of other imaging findings. The final metastatic status was based on the consensus reading, clinical and imaging follow-up (minimal and maximal follow-up time was 6, and 32 months, respectively). The bone findings were compared on patient-, region-, and lesion-level. Results. 99mTc-HDP BS was false negative in four patients. In the region-based analysis, sensitivity values for 99mTc-HDP BS, 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT, and wbMRI+DWI were 62%, 74%, 85%, 93%, and 91%, respectively. The number of equivocal findings for 99mTc-HDP BS, 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT and wbMRI+DWI was 50, 44, 5, 6, and 4, respectively. Conclusion. wbMRI+DWI showed similar diagnostic accuracy to 18F-NaF PET/CT and outperformed 99mTc-HDP SPECT/CT, and 99mTc-HDP BS.

Uptake and Metabolism of Hydroxymatairesinol in Relation to Its Anticarcinogenicity in DMBA-Induced Rat Mammary Carcinoma Model

The chemopreventive effects of hydroxymatairesinol (HMR), a lignan extracted from Norway spruce (Picea abies), on the development of mammary carcinoma induced by 7,12-dimethylbenz[a]anthracene (DMBA) was studied in rats. HMR administered via diet in an average daily dose of 4.7 mg/kg body wt starting before DMBA induction reduced tumor volume and tumor growth, but no significant reduction in tumor multiplicity (number of tumors/rat) was observed. The predominant histological type in the control group was type B (well-differentiated adenocarcinoma, 78%). The proportion of type B tumors decreased to 35% in the HMR group, while the type A (poorly differentiated) and type C (atrophic) tumor proportions increased. Anticarcinogenic effects of dietary HMR (4.7 mg/kg) were also evident when the administration started after DMBA induction and was seen as growth inhibition of established tumors. Dietary HMR supplementation significantly increased serum and urinary enterolactone and HMR concentrations but had no significant effect on the uterine weight, suggesting that HMR or its major metabolite enterolactone did not have an antiestrogenic effect. Further studies are warranted to further clarify and verify HMR action and the associated mechanisms in mammary tumorigenesis.

[11C]methionine quantitation in cancer PET studies.

Quantitation of the uptake of positron emitting tracers in cancer patients is still unsettled. A uniform method is needed for comparison of results and for collecting a data base of tumor PET studies. We have measured the tumoral uptake of [11C]methionine in 46 cancer patients using four different methods of analysis. The accumulation of [11C]methionine at 35-40 min after the injection adjusted to the injected dose and body surface area turned out to give similar results as a more complicated method where the uptake rate of [11C]methionine from the plasma to the tumor was calculated (r = 0.92, p less than 0.0001). The results suggest that in clinical [11C]methionine PET studies, 40 min emission scanning with frequent blood sampling is unnecessary. Only a single 5 min emission scan 25-40 min after the injection is required for analysis if the accumulation is adjusted to the injected dose and body surface area.

Adjuvant Capecitabine in Combination With Docetaxel, Epirubicin, and Cyclophosphamide for Early Breast Cancer: The Randomized Clinical FinXX Trial

Importance Capecitabine is not considered a standard agent in the adjuvant treatment of early breast cancer. The results of this study suggest that addition of adjuvant capecitabine to a regimen that contains docetaxel, epirubicin, and cyclophosphamide improves survival outcomes of patients with triple-negative breast cancer (TNBC). Objective To investigate the effect of capecitabine on long-term survival outcomes of patients with early breast cancer, particularly in subgroups defined by cancer estrogen receptor (ER) and progesterone receptor (PR) content, and HER2 content (human epidermal growth factor receptor 2). Design, Setting, and Participants This is an exploratory analysis of the multicenter FinXX randomized clinical trial that accrued 1500 women in Finland and Sweden between January 27, 2004, and May 29, 2007. About half received 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (T+CEF), while the other half received 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (TX+CEX). Data analysis took place between January 27, 2004, and December 31, 2015. Main Outcomes and Measures Recurrence-free survival (RFS). Results Following random allocation, 747 women received T+CEF, and 753 women received TX+CEX. Five patients were excluded from the intention-to-treat population (3 had overt distant metastases at the time of randomization; 2 withdrew consent). The median age of the remaining 1495 patients was 53 years at the time of study entry; 157 (11%) had axillary node-negative disease; 1142 (76%) had ER-positive cancer; and 282 (19%) had HER2-positive cancer. The median follow-up time after random allocation was 10.3 years. There was no significant difference in RFS or overall survival between the groups (hazard ratio [HR], 0.88; 95% CI, 0.71-1.08; P = .23; and HR, 0.84, 95% CI, 0.66-1.07; P = .15; respectively). Breast cancer-specific survival tended to favor the capecitabine group (HR, 0.79; 95% CI, 0.60-1.04; P = .10). When RFS and survival of the patients were compared within the subgroups defined by cancer steroid hormone receptor status (ER and/or PR positive vs ER and PR negative) and HER2 status (positive vs negative), TX+CEX was more effective than T+CEF in the subset of patients with TNBC (HR, 0.53; 95% CI, 0.31-0.92; P = .02; and HR, 0.55, 95% CI, 0.31-0.96; P = .03; respectively). Conclusions and Relevance Capecitabine administration with docetaxel, epirubicin, and cyclophosphamide did not prolong RFS or survival compared with a regimen that contained only standard agents. Patients with TNBC had favorable survival outcomes when treated with the capecitabine-containing regimen in an exploratory subgroup analysis. Trial Registration clinicaltrials.gov Identifier: NCT00114816

Hormonal treatment of advanced breast cancer. A randomized trial of tamoxifen Versus nandrolone decanoate

The response to tamoxifen (TAM) (10 mg to 20 mg twice orally) was compared with the response to nandrolone decanoate (NAN) (50 mg every second week or 100 mg every third week intramuscularly) in this randomized study in previously untreated women with advanced breast cancer. Patients were postmenopausal or postmenopause was induced with irradiation therapy. The two treatment groups were highly similar in different patient characteristics. Of 67 evaluable patients treated with TAM, ten (15%) had a complete or partial remission, 28 (42%) had stabilized disease and 29 (43%) had progressive disease. In the 60 patients treated with NAN, the figures were ten (17%), 22 (37%) and 28 (47%) respectively. The response rates did not differ significantly. Tam was as good as NAN in osseous metastases. Four of 34 patients responded to TAM and three of 38 patients responded to NAN. NAN had a tendency for better response in the treatment of visceral metastases. Six (43%) of 14 patients responded to NAN while only three (14%) of 21 responded to TAM (P = 0.11). The median duration of remission was 24 months in the TAM arm and 17 months in NAN (insignificant). As second line treatment, NAN after TAM gave one complete remission and three partial remissions, but none responded to TAM after NAN. The side‐effects of both drugs were rare and mild. These data indicate that TAM and NAN are comparable in the treatment of advanced breast cancer.

Carboplatin and Etoposide in Extensive Small Cell Lung Cancer

The combination of carboplatin and etoposide was evaluated in 61 previously untreated patients with extensive small cell lung cancer. Treatment was given at four-week intervals with 450 mg/m2 of carboplatin intravenously (i.v.) on day 1 and etoposide 100 mg/m2 i.v. on days 1-3. The response was complete in 5 (9%) and partial in 28 (50%) of the 56 evaluable patients (overall response rate 59%). The median time to progression after response as well as the median survival time in all evaluable patients was 4.6 months. WHO grade 3 and 4 leukopenia and thrombocytopenia occurred in 8% and 11% of the courses respectively. Two treatment-related deaths were registered. The combination of carboplatin and etoposide used in the present study produced acceptable response rate and toxicity, but duration of response and median survival were shorter than expected from earlier studies.