Prognostic value of monitoring tumour markers CA 15-3 and CEA during fulvestrant treatment.

BACKGROUND: At many centres tumour markers are used to detect disease recurrence and to monitor response to therapy in patients with advanced disease, although the real value of serial observation of marker levels remains disputed. In this study, we evaluated the prognostic value of tumour markers for predicting response (partial response [PR], stable disease [SD] > or = 6 months), de novo disease progression (PD) and secondary PD in patients receiving fulvestrant ('Faslodex') 250 mg/month for the treatment of metastatic breast cancer (MBC). METHODS: Changes in cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) were prospectively monitored (monthly) and were also evaluated for the 3 months preceding secondary PD. Data from 67 patients with previously treated MBC participating in a Compassionate Use Programme were analysed. RESULTS: In patients with a PR (n = 7 [10.4%]), a non-significant increase in CA 15-3 occurred during the first 6 months of treatment; CEA was significantly reduced (P = 0.0165). In patients with SD >/= 6 months (n = 28 [41.8%]), both CA 15-3 (P < 0.0001) and CEA (P = 0.0399) levels increased significantly after 6 months treatment. In those experiencing de novo PD (n = 32 [47.8%]), CA 15-3 increased significantly (P < 0.0001) after 4 months; CEA also increased significantly (P = 0.0002) during the same time period. Both CA 15-3 (P < 0.0001) and CEA (P < 0.0001) increased significantly in the 3 months preceding secondary PD. CONCLUSION: CA 15-3 increases in patients progressing on fulvestrant but may also increase in those experiencing clinical benefit; this should not be taken as a sign of PD without verification. Overall, both CA 15-3 and CEA appear to be poor prognostic markers for determining progression in patients receiving fulvestrant.

Analysis of trastuzumab and chemotherapy in advanced breast cancer after the failure of at least one earlier combination: an observational study.

BACKGROUND: Combining trastuzumab and chemotherapy is standard in her2/neu overexpressing advanced breast cancer. It is not established however, whether trastuzumab treatment should continue after the failure of one earlier combination. In this trial, we report our experience with continued treatment beyond disease progression. METHODS: Fifty-four patients, median age 46 years, range 25-73 years, were included. We analysed for time to tumour progression (TTP) for first, second and beyond second line treatment, response rates and overall survival. RESULTS: Median time of observation was 24 months, range 7-51. Response rates for first line treatment were 7.4% complete remission (CR), 35.2% partial remissions (PR), 42.6% stable disease > 6 months (SD) and 14.8% of patients experienced disease progression despite treatment (PD). Corresponding numbers for second line were 3.7% CR, 22.2% PR, 42.6% SD and 31.5% PD; numbers for treatment beyond second line (60 therapies, 33 pts 3rd line, 18 pts 4th line, 6 pts 5th line, 2 pts 6th line and 1 patient 7th line) were 1.7% CR, 28.3% PR, 28.3% SD and 41.6% PD respectively. Median TTP was 6 months (m) in the first line setting, and also 6 m for second line and beyond second line. An asymptomatic drop of left ventricular ejection fraction below 50% was observed in one patient. No case of symptomatic congestive heart failure was observed. CONCLUSION: The data presented clearly strengthen evidence that patients do profit from continued trastuzumab treatment. The fact that TTP did not decrease significantly from first line to beyond second line treatment is especially noteworthy. Still, randomized trials are warranted.

Oral vinorelbine alone or in combination with trastuzumab in advanced breast cancer: results from a pilot trial.

INTRODUCTION: We evaluated the efficacy of oral vinorelbine (OV) (Navelbine oral Boeringer-Ingelheim Austria) in patients with advanced breast cancer as first-line therapy or after progressing under earlier line chemotherapies alone or in combination with trastuzumab (T). PATIENTS AND METHODS: Seventy-eight patients [median age: 63.5 years (y), range (r): 38-84 years] were included into this trial. Patients with her-2/neu positive tumours received a combination of OV and T. Treatment effect was evaluated every three cycles and treatment continued until progression. OV was administered in a dose of 60 mg/m(2) on day 1 and 8, q = 21 days, and no dose escalation to 80 mg/m(2) was performed. RESULTS: We observed a complete response in 5.9% of patients, partial remission in 22.1%, stable disease (SD) > 6 months in 33.8%, SD < 6 months in 2.9%, and progression despite treatment in 35.3%, respectively. Time to progression was 6 months (range 1-23+). The main toxicities consisted of nausea/vomiting (N/V) and neutropenia. Grade IV neutropenia was found in 5 patients (6.4%), grade III in 6 patients (7.7%) and grade I and II in 11.5%. We did not find any grade IV N/V in our patients, however, grade III N/V was observed in 3.8%. No other grade III and IV toxicities were reported. CONCLUSION: OV appears to be effective in the treatment of advanced breast cancer at the dose and schedule chosen. It is well tolerated, effective, and the oral formulation is an advantage for the patients as well as for the nursing staff.

Preoperative second-line chemotherapy induces objective responses in primary breast cancer.

PURPOSE: Preoperative chemotherapy in patients with primary breast cancer results in high response rates, allowing breast-conserving surgery in patients primarily not suitable for this procedure. Tumors of patients with histologically proven breast cancer that fail to respond to preoperative chemotherapy are thought to be chemotherapy resistant. We questioned this hypothesis and treated 13 patients who did not respond to preoperative anthracycline-containing first-line treatment. PATIENTS AND METHODS: Eight patients received a combination therapy consisting of epidoxorubicin and docetaxel as neoadjuvant first-line treatment and were treated with CMF as preoperative second-line chemotherapy. The other five patients did not respond to first-line FEC and were given paclitaxel or docetaxel as second-line treatment. RESULTS: A major response to treatment was observed in 10 of 13 patients (77%) during preoperative second-line therapy: one patient (8%) achieved pathological complete response (pCR) and nine patients (69%) partial response (PR). Three patients (23%) had stable disease (SD), and no patient had progressive disease (PD). Eight patients (62%) could undergo breast-conserving surgery. CONCLUSIONS: We conclude that it is possible to achieve objective responses including pCR with potentially non-cross-resistant neoadjuvant second-line therapy, leading to breast-conserving surgery in a high proportion of patients. Thus, preoperative second-line chemotherapy appears to be justified when breast conservation is an important treatment goal and may have potential in improved tailoring of neoadjuvant treatments.

Preoperative therapy with epidoxorubicin and docetaxel plus trastuzumab in patients with primary breast cancer: a pilot study.

PURPOSE: Combining anthracyclines and taxanes are to date the most active cytotoxic treatment option in the neoadjuvant and palliative therapy of breast cancer patients. Adding trastuzumab to these cytotoxic agents can improve outcome for women with human epidermal growth factor receptor 2 (HER2)-overexpressing advanced breast cancer. We conducted a pilot study of preoperative epidoxorubicin and docetaxel plus trastuzumab in outpatient patients suffering from breast cancer. PATIENTS AND METHODS: Fourteen consecutive patients were enrolled in this prospective clinical pilot trial. Preoperative treatment consisted of weekly trastuzumab (4 mg/kg body-weight loading dose, 2 mg/kg/week maintenance dose), in combination with weekly epidoxorubicin (30 mg/m2 body surface area [BSA]) and docetaxel (35 mg/m2 BSA) once a week for 6 weeks followed by 1 week off therapy. RESULTS: Patients received a total of 30 cycles (median: 2 cycles, range: 2-3 cycles) of this therapeutic regimen. Outpatient epidoxorubicin and docetaxel plus trastuzumab were well tolerated. A major response to this preoperative therapy regimen could be demonstrated in 12 of 14 patients (86%) leading to breast-conserving surgery in 11 of 14 patients (79%). CONCLUSIONS: We conclude that outpatient epidoxorubicin and docetaxel plus trastuzumab are safe in the neoadjuvant treatment of patients suffering from breast cancer, based on a favorable side-effect and activity profile. Thus, this regimen can be considered for further clinical trials.

Invasive ductal carcinoma and invasive lobular carcinoma of breast differ in response following neoadjuvant therapy with epidoxorubicin and docetaxel + G-CSF.

PURPOSE: Preoperative chemotherapy in patients with primary breast cancer treated with anthracyclines and taxanes results in high response rates, allowing breast conserving surgery (BCS) in patients primarily not suitable for this procedure. Pathological responses are important prognostic parameters for progression free and overall survival. We questioned the impact of histologic type invasive ductal carcinoma (IDC) versus invasive lobular carcinoma (ILC) on response to primary chemotherapy. PATIENTS AND METHODS: 161 patients with breast cancer received preoperative chemotherapy consisted of epidoxorubicin 75 mg/m(2) and docetaxel 75 mg/m(2) administered in combination with granulocyte-colony stimulating factor (G-CSF) on days 3-10 (ED + G). Pathological complete response (pCR), biological markers and type of surgery as well as progression free and overall survival were compared between IDC and ILC. RESULTS: Out of 161 patients, 124 patients presented with IDC and 37 with ILC. Patients with ILC were less likely to have a pCR (3% vs. 20%, P < 0.009) and breast conserving surgeries (51% vs. 79%, P < 0.001). Patients with ILC tended to have oestrogen receptor positive tumors (86% vs. 52%, P < 0.0001), HER 2 negative tumors (69% vs. 84%), and lower nuclear grade (nuclear grade 3, 16% vs. 46%, P < 0.001). Patients with ILC tended to have longer time to progression (TTP) (42 months vs. 26 months) and overall survival (69 months vs. 65 months). CONCLUSIONS: Our results indicate that patients with ILC achieved a lower pCR rate and ineligibility for BCS to preoperative chemotherapy, but this did not result in a survival disadvantage. Because of these results new strategies to achieve a pCR are warranted.

Darbepoetin alpha as treatment for anemia in patients receiving chemotherapy: a single-center experience.

We evaluated Darbepoetin alpha (Aranesp; Amgen), a novel erythropoietic protein, in patients who developed anemia while receiving chemotherapy. Seventy-five patients (median age 62 years, range 40-81 years) undergoing different cancer chemotherapy regimens were treated with darbepoetin alpha. Therapy was started if hemoglobin (Hb) levels fell below 10 g/dl or if symptomatic anemia developed. Treatment effect was evaluated after 4 weeks, 8 weeks and at the end of therapy (up to 12 weeks). If no increase in Hb was seen after 4 weeks, the dose of darbepoetin alpha was increased to 300 microg. Patients were questioned about fatigue and any change during treatment, with evaluation according to a four-point scale, where 0 = no fatigue and 3 = severe fatigue. We observed a treatment response in 54 of 75 patients (72%). Dose escalation was necessary in 30 of 75 patients (40%) and blood transfusions were required in 13 of 75 patients (17.3%). Response was observed in 32 of 43 patients (74.4%) who had a baseline Hb < 10 g/dl and in 22 of 32 (68.8%) patients who had a baseline Hb > or =10 g/dl. At baseline, 60 of 75 patients (93.3%) reported fatigue of grade 2 or 3, but at the end of the 12-week follow-up period, only 26 of 68 patients (38.3%) reported fatigue at these levels. We conclude that darbepoetin alpha is a highly effective and well-tolerated drug in the treatment of chemotherapy-associated anemia. Patients benefited both in terms of Hb levels and control of chemotherapy-related symptoms.

Preoperative chemotherapy with epidoxorubicin, docetaxel and capecitabine plus pegfilgrastim in patients with primary breast cancer.

The objective of this pilot trial was to evaluate the safety and activity profile of epidoxorubicin, docetaxel and oral capecitabine plus pegfilgrastim (TEX+P) as preoperative first-line treatment for patients with breast cancer. Eleven consecutive patients were enrolled in this prospective clinical pilot trial. Preoperative treatment consisted of epidoxorubicin [75 mg/m2 body surface area (BSA)] and docetaxel (75 mg/m2 BSA) administered sequentially on day 1 in combination with oral capecitabine 2000 mg/m2 daily divided into two doses on days 1-14 of each 3-week treatment cycle. Pegfilgrastim 6 mg fixed dose was administered s.c. on day 2 of every treatment cycle. Patients received a total of 58 cycles (median 6 cycles, range 1-6) of this therapeutic regimen. Outpatient TEX+P was well tolerated. No WHO grade IV toxicity was observed. A pathological major response to this preoperative therapy regimen could be demonstrated in eight of nine evaluable patients leading to breast-conserving surgery in seven of nine evaluable patients. We conclude that outpatient TEX+P is safe in the neoadjuvant treatment of patients with primary breast cancer. Thus, this regimen can be considered for further clinical trials.

Zoledronate in a patient with pamidronate refractory hypercalcemia syndrome.

Hypercalcemia of malignancy remains a common metabolic complication of advanced cancer often resulting in considerable morbidity and diminishing life quality in the later stages of disease. Bisphosphonates, especially zoledronic acid, are potent inhibitors of bone resorption and are the most effective therapy for hypercalcemia of malignancy. We report on the course of disease in a 51-year-old woman who presented with metastatic breast cancer that had relapsed to the liver. The patient suffered from a pamidronate-refractory paraneoplastic hypercalcemia, which caused a confused mental status and compromised her already severely limited life quality. Only with the introduction of zoledronate could the patient's hypercalcemia be normalized with consecutive regain of an acceptable life quality.

Capecitabine monotherapy and in combination with immunotherapy in the treatment of metastatic renal cell carcinoma.

This prospective trial aimed to evaluate the therapeutic effects and systemic toxicities of capecitabine monotherapy and capecitabine treatment combined with biological response modifiers in patients with metastatic renal cell carcinoma. Fifty-four patients suffering from metastatic renal cell carcinoma progressing under first-, second- or third-line treatment entered the trial. Capecitabine was given orally at a dose of 2500 mg/m2 daily divided into two doses for 14 days, followed by a 7-day rest in the monotherapy as well as in the combination treatment. This schedule was repeated in 3-week cycles. The combination therapy consisted of capecitabine and an immunotherapy treatment, which consisted either of interferon (IFN)-gamma1b (100 mg/day) administered consecutively 5 times weekly during weeks 1 and 2, and recombinant interleukin (IL)-2 (4.5 MU/day) administered on 4 consecutive days during weeks 3 and 4, every 6 weeks, or IFN-alpha (6 MioIE/day) administered 3 times a week. Fifty-two patients are now evaluable for response and 54 patients for toxicity. We observed a partial response to treatment in five patients (9.6%), minor response in five patients (9.6%), stable disease in 32 patients (61.6%) and only 10 patients (19.2%) showed continued disease progression despite treatment. Outpatient capecitabine was well tolerated. We did not observe any WHO grade IV toxicities. We conclude that capecitabine monotherapy and capecitabine treatment in combination with biological response modifiers appear to be effective regimens with favorable toxicity profiles in patients with advanced renal cell carcinoma. Capecitabine monotherapy seems to be superior than the combination treatment because of its easier application form.