Prospective non-randomized study of preoperative concurrent platinum plus 5-fluorouracil-based chemoradiotherapy with or without paclitaxel in esophageal cancer patients: long-term follow-up.

Combined modality treatment for esophageal carcinoma seems to improve survival over surgery alone. Different combinations of cytotoxic drugs have been studied to improve antitumor efficacy and limit the toxicity of chemoradiotherapy (CRT) with inconsistent results. We present a prospective study of neoadjuvant CRT with or without paclitaxel in chemotherapy schedule. One hundred seven patients (93 males, 14 females), median age 59 years (range 44-76), with operable esophageal cancer were enrolled. They received the following neoadjuvant therapy: Carboplatin, area under curve (AUC) = 6, intravenously on days 1 and 22, 5-fluorouracil (5-FU), 200 mg/m(2)/day, continuous infusion on days 1 to 42, radiation therapy 45 grays/25fractions/5 weeks beginning on day 1. Forty-four patients (41%) were furthermore non-randomly assigned to paclitaxel 200 mg/m(2)/3 h intravenously on days 1 and 22. Nutritional support from the beginning of the treatment was offered to all patients. Surgery was done within 4-8 weeks after completion of CRT, if feasible. All patients were evaluated for grade 3 plus 4 toxicities: leukopenia (28%), neutropenia (30%), anemia (6%), thrombocytopenia (31%), febrile neutropenia (6%), esophagitis (24%), nausea and vomiting (7%), pneumotoxicity (8%). Seventy-eight patients (73%) had surgery and 63 of them were completely resected. Twenty-two patients (20%) achieved pathological complete remission, and additional 20 (19%) had node-negative and esophageal wall-positive residual disease. There were 10 surgery-related deaths, mostly due to pulmonary insufficiency. Twenty-nine patients were not resected, 15 for early progression, 14 for medical reasons or patient refusal. After a median follow-up of 52 months (range 27-80), median survival of 18.0 months and 1-, 2-, 3- and 5-year survival of 56.7, 37.5, 27.0 and 21% was observed in the whole group of 107 patients. Addition of paclitaxel to carboplatin and continual infusion of FU significantly increased hematologic and non-hematologic toxicity, but treatment results as overall survival or time to progression did not differ significantly in groups with and without paclitaxel. Patients achieving pathological complete remission or nodes negativity after neoadjuvant therapy had favorable survival prognosis, whereas long-term prognosis of node positive patients was poor. Distant metastases prevailed as a cause of the treatment failure. Factors significant for survival prognosis in multivariate analysis were postoperative node negativity, performance status, and grade of dysphagia. Addition of paclitaxel to carboplatin and continual FU significantly increased hematologic and non-hematologic toxicity without influencing efficacy of the treatment. This study confirmed improved prognosis of patients after achieving negativity of nodes. Distant metastases prevailed as cause of the treatment failure. Prospectively, it is important to look for a therapeutic combination with better systemic effect.

[Pelvic infiltrations following amputation procedures for rectal carcinomas]. / Infiltráty v pánvi po amputacních výkonech pro karcinom rekta.

INTRODUCTION: The authors present anatomical division of the rectum and then give a short overview of the rectal surgery development. Currently, even in departments specialized in colorectal surgery, 25-30% of the rectal carcinoma cases must be managed by abdominoperineal amputations. COMPLICATIONS OF AMPUTATION PROCEDURES: The study deals with complications following extirpation of the rectum, like bleeding and its management, inflammatory complications during the healing process or following healing of the perineum. However, pelvic relapses, which in most cases cannot be managed surgically, remain the major therapeutic problem. These cases are indicated for systemic treatment with combinations of cytostatic drugs, eventually for radiotherapy. RESULTS: 324 patients with rectal carcinomas were operated at the 1st Surgical Clinic of the VFN in Prague. In 230 cases, resection was completed, in 94 cases, the rectum was amputated. In 78 cases, sutures of the pelvic floor was conducted, 64 cases healed per primam within 3 weeks, 11 healed per secundam within 3 months. In 16 cases, tamponade with surgical cover sheets and longettes was applied. 70% of these patients healed within 12 weeks of the surgery. In 3 cases, chronic fistules persisted for over 6 months. In 11 cases, locoregional relapses occurred. In 2 cases, radical excision was conducted, the other underwent systemic chemotherapy. CONCLUSION: Good preoperative care of the intestine, ATB prophylaxis and saving surgical technique were the precautions taken with the aim to prevent inflammatory complications. With respect to management difficulties of local relapses following amputations of the rectum, a requirement for total excisioning of the mesorectum on the first operation is substantial.

[Neutron capture therapy in the treatment of glioblastoma multiforme. Initial experience in the Czech Republic]. / Neutronová záchytová terapie v lécbe glioblastoma multiforme. První zkusenosti v Ceské republice.

BACKGROUND: Glioblastoma multiforme is the most frequent primary brain tumor in adults. Despite advances in surgery, radiotherapy and chemotherapy, its treatment remains unsatisfactory with very limited overall survival. In the year 2001, in cooperation with Department of Neurosurgery, Nemocnice Na Homolce and Nuclear Research Institute in Rez, we have started to treat glioblastoma patients with boron neutron capture therapy (BNCT). METHODS AND RESULTS: Cells of malignant brain tumors, especially that of glioblastomas, are able to accumulate boron compounds. If BNCT should be successful, it is necessary to reach selective accumulation of sufficient amount of 10B in the tumor and low accumulation in the normal brain tissue. After BSH administration, radiation with low energy thermal neutrons is delivered. It results in nuclear capture and fission reactions with subsequent selective damage of tumor cells. At the time of analysis 9 patients have been enrolled. Therapy was completed in 5 patients. Treatment has been very well tolerated. We observed minimal acute toxicity associated with radiation and no laboratory abnormalities after administrations of BSH. Unfortunately treatment results were quite unsatisfactory. The median time to progression and overall survival were shorter then expected with conventional treatment. CONCLUSIONS: BNCT is very well tolerated with only a modest toxicity. In contrast to standard radiation, BNCT patients receive only one dose of radiation. Nevertheless, in this small pilot study first results were inferior when compared either to outcomes of conventional therapy or to results reported from other BNCT groups. It might be explained that lower dose of radiation had been used. Further study will show whether the higher dose radiation can improve treatment results.

[Tamoxifen or tamoxifen in combination with chemotherapy in adjuvant therapy of breast carcinoma. Results of a multicenter randomized study]. / Tamoxifen nebo tamoxifen v kombinaci s chemoterapií v adjuvantní lécbe karcinomu prsu. Výsledky multicentrické randomizované studie.

UNLABELLED: Between April 1994 and May 1997 103 breast cancer patients (pts), pT1c-3a, pN0-1, M0, were randomised after surgery to adjuvant tamoxifen (20 mg per day) or to tamoxifen plus CMF (C 500 mg/m2, M 40 mg/m2 and F 600 mg/m2 on days 1st and 8th q 28 day) in 6 cycles. The median age (49-72 years, median 58), tumour size, number of involved lymphnodes (0-3), estrogens receptor status, grade (I-III) and type of operation were well balanced among the 50 pts on tamoxifen and the 53 pts on tamoxifen plus CMF pts, preferably postmenopausal. RESULTS: Grade of toxicity according to WHO criteria was not higher then two in both arms. Toxicity both haematological and non-haematological was higher in the group treated with chemotherapy (0 vs 32 resp. 20%) except weight gain (52% in both group). After median follow-up of 42 mos five recurrences in tamoxifen and seven in tamoxifen plus CMF pts were observed (p = NS). The projected 3-y DFS is 92% for tamoxifen and 88% for tamoxifen plus CMF (p = NS). The 3-y OS is 88% for tamoxifen and 80% for tamoxifen plus CMF pts (p = NS). CONCLUSIONS: Both regimens are equally effective with higher toxicity in the group with combined chemo- and hormonal therapy.

[Comparison of adjuvant chemotherapy in breast carcinoma with a combination of cyclophosphamide, methotrexate, 5-fluorouracil (CMF) and AC (doxorubicin, cyclophosphamide). Initial results of a national cooperative study]. / Srovnání adjuvantní chemoterapie karcinomu prsu kombinací cyklofosfamid, metotrexat, 5-fluorouracil (CMF) a AC (doxorubicin, cyklofosfamid). První výsledky národní kooperativní studie.

The aim of this multicentric, prospective randomized trial is to evaluate and to compare, effects and toxicities of two chemotherapeutic combinations (AC and CMF) in adjuvant treatment of breast cancer. Both combinations were given in equitoxic doses and number of cycles was only four. There are 106 women treated for breast cancer T1c-3a, N0-1, M0 in the study. After surgery the patients were randomized, 54 for AC combination and 52 for CMF. We evaluate toxicity of this treatment in all patients in the study. Hematological and nonhematological side effects were comparable in both groups except alopecia (in the group AC was 100%). The study is not finished yet. Preliminary analysis does not show any difference between these two groups.