FEC Therapy Research Articles

Patient Profile and Survival Rate of Breast Cancer Patients with FEC Chemotherapy Regimen at H. Adam Malik Hospital

Breast cancer is a prevalent disease that impacts public health worldwide, including Indonesia. There are various chemotherapy regimens that are currently available. One widely utilized chemotherapy regimen for breast cancer is the FEC regimen, which combines 5-fluorouracil, epirubicin, and cyclophosphamide. This study provides a study of patient profiles and survival rates among breast cancer patients undergoing FEC chemotherapy at H. Adam Malik Hospital. The study utilized a descriptive-retrospective approach with data collected from the medical records of patients who underwent FEC therapy at RSUP H. Adam Malik during January-December 2019. A total of 157 patients were administered anthracycline-based treatment, with 54 patients receiving FEC (34.39%). The majority of individuals under the FEC regimen were primarily luminal B (51.75%) and IBC (33.33%). The survival rate for individuals using the FEC chemotherapy regimen was found to be 37.98 months. Additionally, patients with risk factors associated with invasive breast cancer (IBC) exhibited a 1.20-fold increased risk of mortality compared to individuals with other forms of breast cancer. The first-line FEC chemotherapy regimen continues to be a feasible therapeutic option for subtypes of breast cancer, and there is no discernible variation in survival rate observed across these characteristics.

Search for nutritional and inflammatory marker ratios to predict neutropenia in FEC therapy for breast cancer: Aretrospective observational study.

Nutritional and inflammatory marker ratios are known to predict response to chemotherapy in breast cancer, but whether they predict adverse effects caused by chemotherapy remains unclear. We investigated whether nutritional and inflammatory marker ratios before starting FEC therapy (5-fluorouracil, epirubicin, and cyclophosphamide) predict grade 4 neutropenia as a serious adverse effect. 61 patients with breast cancer who started FEC therapy for the first time as preoperative or postoperative chemotherapy were studied. Relevant nutritional and inflammatory marker ratios were compared between patients who developed grade 4 neutropenia (n = 44) and those who did not (n = 17). In univariate analysis, occurrence of neutropenia was related significantly (p<0.05) to pre-FEC-therapy white blood cell count, platelet count, neutrophil count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and modified Glasgow prognostic score. Analysis using cutoff values obtained from receiver operating characteristic curves showed that LMR, NLR, and PLR predicted grade 4 neutropenia. However, multivariate logistic regression analysis identified no independent factor associated with grade4 neutropenia. A post-hoc power analysis revealed an inadequate sample size. Inflammatory marker ratios, especially PLR, may predict grade 4 neutropenia caused by FEC therapy for breast cancer. Although multivariate analysis identified no independent predictive markers in this study due to inadequate sample size, further prospective large-scale research is needed to examine the usefulness of nutritional and inflammatory marker ratios for predicting adverse effects.

Chemotherapy resumption in breast cancer patient after COVID-19

BackgroundWhile many studies have verified the effect of recent anti-cancer treatment in patients with COVID-19, there are no data on the optimal time for cancer treatment resumption, as well as the safety of chemotherapy in COVID-19 patients. As many cancer patients are recovering from COVID-19, there is an urgent need for reliable clinical information. Herein, we report a case of invasive ductal carcinoma in which we were able to successfully resume chemotherapy after infection with SAR-CoV-2.Case presentationThe patient was a 38-year-old non-smoking Japanese woman with no significant medical history. She had fever on days 5 and 6 of her second course of adjuvant FEC therapy, and on day 7, she tested positive for SARS-CoV-2 by RT-PCR. She was hospitalized for 11 days. We resumed the therapy on day 25 after discharge, as she had no remaining clinical symptoms. The patient completed four courses of the initial chemotherapy without any major adverse events nor the recurrence of COVID-19, and subsequently completed four courses of docetaxel as her second regimen therapy.ConclusionsEvaluating the risk for each patient is essential when resuming anti-cancer therapy in cancer patient’s post-COVID-19.

Abstract PS16-31: SKT11 loss drives rapid cancer progression and fatal pulmonary tumor thrombotic microangiopathy (PTTM) in a breast cancer patient: A case report

Abstract Introduction: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare cancer-associated respiratory complication characterized by widespread tumor cell emboli in small arteries and arterioles of the lung. Breast cancer is the second most common cancer causing PTTM. The pathogenesis and molecular background of PTTM have not been clarified. Here we present a case of breast cancer that experienced early onset of liver metastasis after surgical resection of the primary tumor and rapid progression leading to death due to severe respiratory distress. Autopsy was performed and it revealed that the main cause of her death was PTTM. Comprehensive next generation sequencing (NGS) analysis of the tissue obtained serially during the clinical course was performed. Case Presentation: A 48-year-old woman was diagnosed with invasive ductal carcinoma of the left breast, which was ER positive, PgR negative, and HER2 negative. FEC followed by docetaxel was administered as preoperative chemotherapy. Her tumor dramatically shrunk with chemotherapy and left partial mastectomy with left axillary lymph node dissection was performed. Histopathological analysis of the resected breast tissue revealed that there were a lot of residual cancer cells, which were ER negative, PgR negative, HER2 negative, and the result indicated that response to preoperative chemotherapy was insufficient. Additional two courses of FEC therapy were performed. Postoperative radiation therapy including the left supraclavicular lymph node area was given and adjuvant endocrine therapy with anastrozole started at the same time. At 3 months of anastrozole administration, she presented hepatic dysfunction and abnormal CT findings in the liver. Liver biopsy revealed multiple liver metastasis of breast cancer. Unresponsive to weekly paclitaxel and bevacizumab, she developed rapid respiratory failure leading to her death in two weeks. Postmortem microscopic analysis revealed an intimal fibrocellular proliferation in the pulmonary arterioles regardless of microscopic tumor emboli and extensive sinusoidal metastasis of the whole liver. NGS Analysis: We analyzed four specimens, breast cancer biopsy specimen at diagnosis, surgical resection specimen, liver needle biopsy specimen, and liver specimen obtained at autopsy, with the Ion AmpliSeq Comprehensive Cancer Panel (Thermo Fisher). The results were compared with NGS analysis of her normal lung tissue to exclude single nucleotide polymorphisms. Deep sequencing revealed that only TP53 R213* was detected as an oncogenic mutation in all four specimens. There were no mutations associated with the development of liver metastasis and her death. Comparison of the samples obtained between before and after liver metastasis revealed that STK11 loss and IKBKE amplification were harbored only in the specimens after liver metastasis. RNA sequencing analysis with the samples of initial biopsy and liver biopsy showed that the RNA expression associated with apoptosis and adhesion molecules was strongly suppressed in the liver sample. Conclusion: STK11 encodes a serine/threonine kinase, which organizes cell polarity and inhibits tumor growth. In the present patient, STK11 loss had occurred during the treatment and could induce rapid progression of her disease and PTTM. Citation Format: Fumie Fujisawa, Kei Kunimasa, Rieko Kano, Hiroki Kusama, Minako Nishio, Saki Matsui, Tetsuhiro Yoshinami, Nobuyoshi Kittaka, Shigenori Nagata, Toshinari Yagi, Takahiro Nakayama, Yasuhiro Tamaki, Fumio Imamura. SKT11 loss drives rapid cancer progression and fatal pulmonary tumor thrombotic microangiopathy (PTTM) in a breast cancer patient: A case report [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-31.

Evaluation of CINV in Multiple Courses of FEC and EC Therapy in Japanese Breast Cancer Patients

Evaluation of CINV in Multiple Courses of FEC and EC Therapy in Japanese Breast Cancer Patients

Phase II study of neoadjuvant anthracycline combined with nanoparticle albumin‑bound paclitaxel for human epidermal growth factor receptor 2‑negative breast cancer

Neoadjuvant chemotherapy (NAC) with anthracyclines followed by taxane chemotherapy has become the standard treatment for patients with locally advanced, operable breast cancer. Recently, the efficacy of nanoparticle albumin-bound paclitaxel (nab-PTX) for metastatic breast cancer was reported. However, there are still few studies of a neoadjuvant regimen including nab-PTX. Thus, the present phase II study evaluated the efficacy and safety of 5-fluorouracil, epirubicin and cyclophosphamide (FEC regimen) followed by nab-PTX as neoadjuvant treatment for operable human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Women with operable HER2-negative breast cancer (clinical stage T1a-4N1-3) received 4 cycles of FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 every 21 days), followed by 4 cycles of nab-PTX at 260 mg/m2 every 21 days. The patients then underwent mastectomy or breast-conserving surgery (BCS). The primary endpoint was pathological complete response (pCR) rate. The secondary endpoints included clinical response rate, pathological response rate, BCS rate and safety. A total of 16 patients were evaluated and 3 patients (18%) achieved pCR (1 patient with estrogen receptor-positive cancer and 2 with estrogen receptor-negative cancer). The pCR rate was 12 and 25% in patients with estrogen receptor-positive and -negative cancers, respectively. The clinical response rate was 100% (clinical complete and partial response in 6 and 10 patients, respectively). The BCS rate was 31.25%. Three patients experienced grade 3 neutropenia during FEC therapy, and no grade 3/4 events occurred during nab-PTX therapy. Thus, neoadjuvant therapy with FEC followed by nab-PTX for operable HER2-negative breast cancer was found to be a safe and effective option.

CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial

CT-P6 is a proposed biosimilar to reference trastuzumab. In this study, we aimed to establish equivalence of CT-P6 to reference trastuzumab in neoadjuvant treatment of HER2-positive early-stage breast cancer. In this randomised, double-blind, active-controlled, phase 3 equivalence trial, we recruited women aged 18 years or older with stage I-IIIa operable HER2-positive breast cancer from 112 centres in 23 countries. Inclusion criteria were an Eastern Cooperative Oncology Group performance status score of 0 or 1; a normal left ventricular ejection fraction of at least 55%; adequate bone marrow, hepatic, and renal function; at least one measureable lesion; and known oestrogen and progesterone receptor status. Exclusion criteria included bilateral breast cancer, previous breast cancer treatment, previous anthracycline treatment, and pregnancy or lactation. We randomly allocated patients 1:1 to receive neoadjuvant CT-P6 or reference trastuzumab intravenously (eight cycles, each lasting 3 weeks, for 24 weeks; 8 mg/kg on day 1 of cycle 1 and 6 mg/kg on day 1 of cycles 2-8) in conjunction with neoadjuvant docetaxel (75 mg/m2 on day 1 of cycles 1-4) and FEC (fluorouracil [500 mg/m2], epirubicin [75 mg/m2], and cyclophosphamide [500 mg/m2]; day 1 of cycles 5-8) therapy. We stratified randomisation by clinical stage, receptor status, and country and used permuted blocks. We did surgery within 3-6 weeks of the final neoadjuvant study drug dose, followed by an adjuvant treatment period of up to 1 year. We monitored long-term safety and efficacy for 3 years after the last patient was enrolled. Participants and investigators were masked to treatment until study completion. The primary efficacy endpoint, analysed in the per-protocol population, was pathological complete response, assessed via specimens obtained during surgery, analysed by masked central review of local histopathology reports. The equivalence margin was -0·15 to 0·15. This trial is registered with ClinicalTrials.gov, number NCT02162667, and is ongoing, but no longer recruiting. Between Aug 7, 2014, and May 6, 2016, we randomly allocated 549 patients (271 [49%] to CT-P6 vs 278 [51%] to reference trastuzumab). A similar proportion of patients achieved pathological complete response with CT-P6 (116 [46·8%; 95% CI 40·4-53·2] of 248 patients) and reference trastuzumab (129 [50·4%; 44·1-56·7] of 256 patients). The 95% CI of the estimated treatment outcome difference (-0·04% [95% CI -0·12 to 0·05]) was within the equivalence margin. 19 (7%) of 271 patients in the CT-P6 group reported serious treatment-emergent adverse events versus 22 (8%) of 278 in the reference trastuzumab group; frequent (occurring in more than one patient) serious adverse events were febrile neutropenia (four [1%] vs one [<1%]) and neutropenia (one [<1%] vs two [1%]). Grade 3 or worse treatment-related adverse events occurred in 17 (6%) of 271 patients in the CT-P6 group versus 23 (8%) of 278 in the reference trastuzumab group; the most frequently reported adverse event was neutropenia in ten (4%) versus 14 (5%). CT-P6 showed equivalent efficacy to reference trastuzumab and adverse events were similar. Availability of trastuzumab biosimilars could increase access to this targeted therapy for HER2-positive early-stage cancer. Celltrion Inc.

P2-127 - Pneumocystis Pneumonia in Patients with Solid Tumors during Chemotherapy

ABSTRACT Background Pneumocystis pneumonia (PCP) is an opportunistic infection well recognized in patients with profound T cell immunodeficiency, especially in patients with AIDS. This infection is also a life-threatening complication seen during immunosuppressive chemotherapy for cancer or organ transplantation, so it is important to make an early diagnosis and start treatment. We present three cases of PCP developing during chemotherapy for solid malignancies. Case reports Case 1: A 50-year-old female received a first-line chemotherapy of gemcitabine–docetaxel (GT therapy) for leiomyosarcoma. After three cycles of GT therapy, she was admitted for a non-productive cough and high fever. Her chest radiograph and CT showed diffuse ground-glass bilateral opacities. SpO2 was 90% (room air). Serum b- d -glucan was 66.7 pg/ml. PCR of PCP by using BAL specimens was positive. We diagnosed PCP infection. Case 2: A 70-year-old female received gemcitabine (GEM) monotherapy as a first-line treatment of a pancreas cancer. After two cycles of GEM therapy, she developed dyspnea and a fever of 38°C. Her chest radiograph and CT showed diffuse ground-glass bilateral opacities. SpO2 was 92% (room air). Serum b- d -glucan was 40.8 pg/ml. We diagnosed PCP infection on the basis of these findings. Case 3: A 64-year-old female received neo-adjuvant chemotherapy with 5-fluoropyrimidine, epirubicin and cyclophosphamide (FEC therapy) for a breast cancer. After two cycles of FEC therapy, she was admitted for febrile neutropenia. Although neutropenia was recovered, she developed exertional dyspnea and a non-productive cough with continuous high fever. Her chest CT showed diffuse ground-glass bilateral opacities. SpO2 was 90% (room air). Serum b- d -glucan was 39.5 pg/ml. We diagnosed PCP infection on the basis of these findings. These patients were immediately treated with trimethoprim–sulfamethoxazole (ST) and corticosteroid. The infiltrations and diffuse ground-glass opacities on their chest radiographs improved and they got well. Conclusion We should be careful of not only drug-induced interstitial pneumonia and febrile neutropenia but also PCP during chemotherapy for solid malignancies.

Dose-tailoring of FEC adjuvant chemotherapy based on leukopenia is feasible and well tolerated. Toxicity and dose intensity in the Scandinavian Breast Group phase 3 adjuvant Trial SBG 2000-1

The SBG 2000-1 trial is a randomised study that investigates if dose-tailored adjuvant FEC therapy based on the individual's leukocyte nadir value can improve outcome. The study has included 1535 women with medium and high-risk breast cancer. Patients and methods. After a first standard dosed FEC course (5-fluorouracil 600 mg/m2, epirubicin 60 mg/mg2 and cyclophosphamide 600 mg/m2), patients who did not reach leukopenia grade III or IV were randomised to standard doses (group standard) or doses tailored to achieve grade III leukopenia (group tailored) at courses 2–7. Patients who achieved leukopenia grade III or more after the first course were not randomised but continued on standard doses (group registered). Results. Both planned and actually delivered number of courses (seven) were the same in all three arms. The relative dose intensity was increased by a factor of 1.31 (E 1.22, C 1.43) for patients in the tailored arm compared to the expected on standard dose. Ninety percent of the patients in the tailored arm achieved leukopenia grade III–IV compared with 29% among patients randomised to standard dosed therapy. Dose tailoring was associated with acceptable acute non-haematological toxicity with more total alopecia, nausea, vomiting and fatigue. Conclusion. Dose tailoring according to leukopenia was feasible. It led to an increased dose intensity and was associated with acceptable excess of acute non-haematological toxicity.

CHER LOB Trial: Preoperative chemotherapy plus trastuzumab, lapatinib or both in HER2-positive operable breast cancer—Safety report as per Independent Data Monitoring Committee (IDMC) and preliminary activity data

580 Background: We conducted a phase IIb randomized trial of preoperative chemotherapy (CT) plus trastuzumab (T), lapatinib (L), or the combination of T+L in HER2+ operable breast cancer > 2cm. Primary endpoint is the % of pathologic complete response (pCR) in breast and axillary nodes. Secondary endpoints: breast objective response, % of breast conservative surgery, safety, molecular responses, gene expression related to pCR. Methods: Patients with HER2+ stage II-IIIA breast cancer are randomized to Arm A: CT+T; Arm B: CT+L; Arm C: CT+T+L. CT consists of paclitaxel (P) 80 mg/m2 weekly for 12 weeks followed by 4 cycles of FE75C q3weeks. T is administered at 2 mg/kg weekly in arms A and C; L is administered at 1,500 mg po daily in arm B, and at 1,000 mg po daily in arm C. Both T and L are administered throughout the duration of CT. Left ventricular ejection fraction (LVEF) is evaluated at baseline, before the start of FEC, and at the completion of treatment. The planned sample size, calculated with the two steps Simon's design, includes 120 patients. Safety analyses by the IDMC are planned at the following time-points: 1) after the first 15 patients treated for ≥3 months; 2) after the first 30 patients treated for ≥3 months. If no safety concerns, further analyses are planned for every 30 patients until study closure. Results: 28 patients have been randomized: 8 in Arm A, 9 in Arm B, 11 in Arm C. A total of 187 doses of weekly P+T, L or T+L, and 46 courses of FEC+T, L or T+L are evaluable. Hematologic toxicity: grade (G) 3–4 neutropenia in 9.6% of weekly P and in 52% of FEC cycles. Nonhematologic toxicity (excluding nausea and vomiting) reported for >5% of cycles were: diarrhea (G1–2: 26%; G3: 4%), G1–2 skin toxicity (23%), and G1 neurotoxicity (10%) during weekly P; G1–2 diarrhea (20%), G1–2 skin toxicity (28%) and G1 neurotoxicity (20%) during FEC therapy. The mean LVEF was 64% (range 54–74%) at baseline, 63% (60–71%) after 12 weeks, and 61% (60–63%) at the end of therapy. Conclusions: The preliminary safety data on the combination of T and L with an anthracycline-containing regimen seem encouraging. The first 2 evaluations as per IDMC and preliminary activity data will be presented at the Meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline

Evaluation of efficacy and safety of neoadjuvant chemotherapy with weekly paclitaxel in patients with locally advanced and large operable breast cancer

11593 Background: Taxanes have been shown to induce high pathologic response rates in patients with early breast cancer. We studied the use of single agent weekly paclitaxel as anterior chemotherapy in large operable (tumour size >5 cm) breast cancer (LOBC) and locally advanced breast cancer (LABC). Methods: In this prospective study, we enrolled women above 18 years with T3–4 any N and N2- 3 any T with nonmetastatic disease. Patients with inadequate organ function were excluded. Tumor size was documented at baseline and after completion of neoadjuvant chemotherapy. After diagnostic biopsy, patients were given paclitaxel (100 mg/m2) weekly for 8 weeks. This was followed by breast conservative surgery or mastectomy (as per surgeon’s discretion) and adjuvant chemotherapy with 4 cycles of FEC (5-fluorouracil 500 mg/m2, epirubicin 90 mg/m2, cyclophosphamide 500 mg/m2), radiotherapy and hormone therapy (if indicated). The primary objectives included assessment of clinical and pathologic response after primary chemotherapy and to assess toxicity profile of weekly paclitaxel. Results: A total of 30 patients - stage IIA-2, stage IIB-1, stage IIIA-8, stage IIIB-18, stage IIIC-1 between the ages of 30–67 were included. All 30 patients were assessable for clinical response and 28 patients were assessable for pathologic response. A total of 239 out of planned 240 cycles were administered. Clinical complete response was seen in 12/30 patients and clinical partial response in 16/30 patients (overall response = 28/30). One patient each had stable and progressive disease. Complete pathologic response was observed in 4 patients. Two patients received second-line chemotherapy owing to suboptimal response. Side effects were mild in the form of myalgia, nausea and vomiting. Eight patients developed Grade I-II neuropathy and 1 patient developed Grade IV neuropathy. No incidence of neutropenic fever was noted during the weekly paclitaxel schedule. One patient suffered from myelotoxicity in the form Grade III leucopenia, Grade IV neutropenia and grade III thrombocytopenia. Conclusions: Single agent weekly paclitaxel is safe and effective as neoadjuvant chemotherapy in patients with LOBC and LABC with modest pathologic responses. No significant financial relationships to disclose.

Quality of life in women with breast cancer randomised to adjuvant treatment with marrow supported high dose chemotherapy with CTCb (BMT) or tailored FEC therapy: The SBG-9401 study

Quality of life in women with breast cancer randomised to adjuvant treatment with marrow supported high dose chemotherapy with CTCb (BMT) or tailored FEC therapy: The SBG-9401 study

Multimodality treatment of 128 patients with locally advanced breast carcinoma in the era of mammography screening using standard polychemotherapy with 5‐fluorouracil, epirubicin, and cyclophosphamide

BACKGROUND Locally advanced breast carcinoma is associated with a poor prognosis. With single treatment modalities, i.e., surgery and/or radiation therapy, results have been consistently dismal. However, several earlier reports have indicated improvement in survival with a combined modality approach, i.e., the utilization of systemic therapy. METHODS Between 1991 and 1994, 128 patients with locally advanced noninflammatory or inflammatory breast carcinoma (LABC) were treated with a combined modality strategy consisting of 4-6 courses of preoperative 5-fluorouracil (600 mg/m2), epirubicin (60 mg/m2), and cyclophosphamide (600 mg/m2) (FEC) every 3 weeks, followed by modified radical mastectomy or sector resection with axillary dissection in combination with postoperative radiotherapy and concomitant cyclophosphamide (850 mg/m2). Postoperatively, 3-5 adjuvant courses of FEC therapy were given. Nine percent of the patients received preoperative radiotherapy because the FEC therapy was not sufficiently effective. One-third of the patients were given tamoxifen (20 or 40 mg daily) at the end of the multimodal therapy. RESULTS Clinical responses were observed in 60% of the patients; 5% had complete responses (CR) and 55% had partial responses (PR). Stable disease (SD) was observed in 40%. No patient had progressive disease (PD) preoperatively. With a median follow-up of 37 months, the median disease free survival (DFS) and median overall survival (OS) were 29 and 54 months, respectively. The actuarial 5-year DFS and OS were 36% and 49%, respectively. The locoregional recurrence rate was 20%, and 53% of the patients experienced systemic relapse. Univariate analysis revealed a significant prognostic difference according to clinical stage of LABC in favor of less advanced stages. Clinical and biologic parameters linked to a significantly worse prognosis were the presence of inflammatory breast carcinoma and peau d'orange. There was a significant trend of worse prognosis for patients receiving below 60% and 75% of the intended dose intensity with reference to DFS and OS, respectively. CONCLUSIONS Standard dose preoperative and postoperative FEC therapy combined with surgery and radiotherapy in the era of mammography screening seem to yield results comparable to those achieved with other conventional strategies in the treatment of unscreened populations. Cancer 1998;83:936-947. © 1998 American Cancer Society.

Multimodality treatment of 128 patients with locally advanced breast carcinoma in the era of mammography screening using standard polychemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide

Locally advanced breast carcinoma is associated with a poor prognosis. With single treatment modalities, i.e., surgery and/or radiation therapy, results have been consistently dismal. However, several earlier reports have indicated improvement in survival with a combined modality approach, i.e., the utilization of systemic therapy. Between 1991 and 1994, 128 patients with locally advanced noninflammatory or inflammatory breast carcinoma (LABC) were treated with a combined modality strategy consisting of 4-6 courses of preoperative 5-fluorouracil (600 mg/m2), epirubicin (60 mg/m2), and cyclophosphamide (600 mg/m2) (FEC) every 3 weeks, followed by modified radical mastectomy or sector resection with axillary dissection in combination with postoperative radiotherapy and concomitant cyclophosphamide (850 mg/m2). Postoperatively, 3-5 adjuvant courses of FEC therapy were given. Nine percent of the patients received preoperative radiotherapy because the FEC therapy was not sufficiently effective. One-third of the patients were given tamoxifen (20 or 40 mg daily) at the end of the multimodal therapy. Clinical responses were observed in 60% of the patients; 5% had complete responses (CR) and 55% had partial responses (PR). Stable disease (SD) was observed in 40%. No patient had progressive disease (PD) preoperatively. With a median follow-up of 37 months, the median disease free survival (DFS) and median overall survival (OS) were 29 and 54 months, respectively. The actuarial 5-year DFS and OS were 36% and 49%, respectively. The locoregional recurrence rate was 20%, and 53% of the patients experienced systemic relapse. Univariate analysis revealed a significant prognostic difference according to clinical stage of LABC in favor of less advanced stages. Clinical and biologic parameters linked to a significantly worse prognosis were the presence of inflammatory breast carcinoma and peau d'orange. There was a significant trend of worse prognosis for patients receiving below 60% and 75% of the intended dose intensity with reference to DFS and OS, respectively. Standard dose preoperative and postoperative FEC therapy combined with surgery and radiotherapy in the era of mammography screening seem to yield results comparable to those achieved with other conventional strategies in the treatment of unscreened populations.

Double-Blind Randomized Trial of Lorazepam versus Placebo with Methylprednisolone for Control of Emesis Due to Non-Cisplatin Containing Chemotherapy

Fifty-three breast cancer patients receiving adjuvant chemotherapy entered a double-blind randomized trial of lorazepam 2.5 mg orally prior to chemotherapy and repeated after 12 hours (Arm A) versus placebo (Arm B) with methylprednisolone (MPN) 375 mg in 3 equal doses: 125 mg i.v. prior to chemotherapy and repeated i.m. 6 and 12 hours later. Adjuvant therapy with 5-fluorouracil 600 mg/m2, 4'-epi-doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2 (FEC) day 1 was alternated every 21 days with cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, 5-fluorouracil 600 mg/m2 (CMF) day 1 for a total of 12 courses. The majority of patients experienced greater than or equal to 5 emetic episodes with FEC therapy (Arm A = 52%; Arm B = 55%). Mild and moderate nausea were reported by 60% and 68% of patients in Arms A and B, respectively. With CMF therapy complete control of emesis was observed in 33% (Arm A) and 35% (Arm B) of patients. The addition of lorazepam did not improve results either with FEC or CMF. Sedation was experienced by 86 to 92% of patients treated with lorazepam and amnesia was observed in 48-50% of cases. FEC therapy must be considered a highly emetic regimen and antiemetic therapy planned accordingly.