White blood cell subsets in HER2-positive breast cancer patients treated with trastuzumab in relation to clinical outcome.

To examine whether HER2+ breast cancer patients who have decreased immune effector cells could respond well to trastuzumab, we evaluated the alterations in circulating immune system cell subsets: CD16+ and/or CD56+ lymphocytes, lymphocytes and granulocytes in these patients before and after treatment with trastuzumab-based regimens in relation to clinical response to therapy. The study involved 55 patients with HER2+ breast cancer before and 2 months after the initiation of the therapy. Progressive disease was confirmed in nine out of 55 patients (non-responders), while other patients achieved complete or partial response, or stable disease (responders). Control group consisted of up to 52 healthy individuals. Significantly lower percentages of total lymphocytes, CD16+, CD56+, and CD16+CD56+ lymphocytes as well as higher percentage of granulocytes and a higher ratio of granulocyte to lymphocyte percentages were found in patients before therapy and 2 months after the initiation of the therapy, compared with those in healthy individuals. Responder subgroup showed significantly lower percentages of CD16+, CD56+, and CD16+CD56+ lymphocytes before therapy, compared with those in healthy controls. Two months after the initiation of the therapy, the percentages of immune cell subsets remained significantly lower in responders in comparison with those in the healthy donors, while a significantly decreased percentages of CD56+ and CD16+CD56+ lymphocytes were observed in non-responders, in comparison with those in healthy controls. Our study demonstrated that HER2+ breast cancer patients who have decreased percentages of CD16+, CD56+, and CD16+CD56+ lymphocytes may achieve response to trastuzumab-containing treatment.

Additional Therapy with a Mistletoe Product during Adjuvant Chemotherapy of Breast Cancer Patients Improves Quality of Life: An Open Randomized Clinical Pilot Trial.

Background. Breast cancer patients receiving adjuvant chemotherapy often experience a loss of quality of life. Moreover chemotherapy may induce neutropenia. Patients report a better quality of life when additionally treated with mistletoe products during chemotherapy. Methods. In this prospective randomized open-label pilot study 95 patients were randomized into three groups. All patients were treated with an adjuvant chemotherapy. The primary objective of the study was quality of life, the secondary objective was neutropenia. Here we report the comparison of HxA (n = 34) versus untreated control (n = 31). Results. In the explorative analysis ten of 15 scores of the EORTC QLQ-C30 showed a better quality of life in the HxA group compared to the control group (P < 0.001 to P = 0.038 in Dunnett-T3 test). The difference was clinically relevant (difference of at least 5 points, range 5.4-12.2) in eight of the ten scores. Neutropenia occurred in 7/34 HxA patients and in 8/31 control patients (P = 0.628). Conclusions. This pilot study showed an improvement of quality of life by treating breast cancer patients with HxA additionally to CAF. Although the open design may be a limitation, the findings show the feasibility of a confirmatory study using the methods described here.

Five-year follow-up of patients with early stage breast cancer after a randomized study comparing additional treatment with viscum album (L.) extract to chemotherapy alone.

Additional therapy with extracts of Viscum album [L.] (VaL) increases the quality of life of patients suffering from early stage breast cancer during chemotherapy. In the current study patients received chemotherapy, consisting of six cycles of cyclophosphamide, anthracycline, and 5-Fluoro-Uracil (CAF). Two groups also received one of two VaL extracts differing in their preparation as subcutaneous injection three times per week. A control group received CAF with no additional therapy. Six of 28 patients in one of the VaL groups and eight of 29 patients in the control group developed relapse or metastasis within 5 years. Subgroup analysis for hormone- and radiotherapy also showed no difference between groups. Additional VaL therapy during chemotherapy of early stage breast cancer patients appears not to influence the frequency of relapse or metastasis within 5 years.

Quality of life and neutropenia in patients with early stage breast cancer: a randomized pilot study comparing additional treatment with mistletoe extract to chemotherapy alone.

BACKGROUND: Chemotherapy for breast cancer often deteriorates quality of life, augments fatigue, and induces neutropenia. Mistletoe preparations are frequently used by cancer patients in Central Europe. Physicians have reported better quality of life in breast cancer patients additionally treated with mistletoe preparations during chemotherapy. Mistletoe preparations also have immunostimulant properties and might therefore have protective effects against chemotherapy-induced neutropenia. PATIENTS AND METHODS: We conducted a prospective randomized open label pilot study with 95 patients randomized into three groups. Two groups received Iscador® M special (IMS) or a different mistletoe preparation, respectively, additionally to chemotherapy with six cycles of cyclophosphamide, adriamycin, and 5-fluoro-uracil (CAF). A control group received CAF with no additional therapy. Here we report the comparison IMS (n = 30) vs. control (n = 31). Quality of life including fatigue was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Neutropenia was defined as neutrophil counts <1,000/µl and assessed at baseline and one day before each CAF cycle. RESULTS: In the descriptive analysis all 15 scores of the EORTC-QLQ-C30 showed better quality of life in the IMS group compared to the control group. In 12 scores the differences were significant (p < 0.02) and nine scores showed a clinically relevant and significant difference of at least 5 points. Neutropenia occurred in 3/30 IMS patients and in 8/31 control patients (p = 0.182). CONCLUSIONS: This pilot study showed an improvement of quality of life by treating breast cancer patients with IMS additionally to CAF. CAF-induced neutropenia showed a trend to lower frequency in the IMS group.

What is the best sequence of chemotherapy in advanced colorectal cancer? Final results of a five-arm study.

One hundred and ninety-three patients were assigned to receive 5-FU/LV, irinotecan and oxaliplatin in five different sequential treatment groups: Mayo Clinic Regimen (MCR) + LV5FU2 (group A); MCR + irinotecan (350 mg/m(2)) (group B); MCR + FOLFIRI (group C); MCR + FOLFOX4 (group D); FOLFIRI + FOLFOX4 (group E). The results were as follows: group A (32 patients), median overall survival (OS) 14 months, median time to progression (TTP1) 6 months, median TTP2 5 months, response rate (RR1) 22%, RR2 25%; group B (27 patients), OS 11 months, TTP1 6 months, TTP2 3 months, RR1 22%, RR2 19%; group C (43 patients), OS 14 months, TTP1 5 months, TTP2 5 months, RR1 12%, RR2 19%; group D (45 patients), OS 15 months, TTP1 5 months, TTP2 4 months, RR1 18%, RR2 20%; group E (46 patients), OS 19 months, TTP1 9 months, TTP2 5 months, RR1 39%, RR2 25%. There was a significant difference in OS (p < 0.005) between groups E vs. B and A, D vs. B. Sequential therapy with 3 active drugs (FOLFIRI + FOLFOX4) was the most efficacious combination in comparison with any other two drug combinations applied in our study.