[Hormonal therapy in breast cancer]. / Tratamiento hormonal del cáncer de mama.

Hormonal therapy has been the first systemic treatment against breast cancer. Up to now Tamoxifen and ovarian supression/ablation were the best optionts we had to treat early breast cancer as advancer disease. The advent of aromatase inhibitors, new SERMS and antistrogen Fulvestrant have supoused a great advance in the treatment of this disease and at the same time have complicated the election of the optimal drug for each patient. This article tries to review the aviable treatment options insiting on its indications.

Primary central nervous system lymphoma treated with rituximab plus temozolomide in a second line schedule.

We report a case of primary CNS lymphoma treated with high-dose methotrexate in the first line. After disease progression the patient received cranial radiotherapy with concomitant temozolomide, followed by rituximab plus temozolomide, with complete remission of the disease maintained for at least two years and without major toxicity.

Primary central nervous system lymphoma treated with rituximab plus temozolomide in a second line schedule

We report a case of primary CNS lymphoma treated with high-dose methotrexate in the first line. After disease progression the patient received cranial radiotherapy with concomitant temozolomide, followed by rituximab plus temozolomide, with complete remission of the disease maintained for at least two years and without major toxicity (AU)

Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study.

The purpose of this trial was to study feasibility and tolerance of a dose-intensive multicyclic alternating induction chemotherapy with repeated stem cell support in a series of 43 metastatic breast cancer patients. Anthracycline-naive patients (n = 21) received cyclophosphamide 2.5 g/m(2) plus doxorubicin 80 mg/m(2) alternating every 14 days with paclitaxel 200-350 mg/m(2) plus cisplatin 120 mg/m(2). Patients who had previously received anthracyclines (n = 22) received cisplatin 120 mg/m(2) plus etoposide 600 mg/m(2) alternating with paclitaxel 200-350 mg/m(2) plus ifosfamide 8 g/m(2). Peripheral blood stem cells were infused after every course except the first, with a median CD34(+) dose of 2.1 x 10(6)/kg per cycle. Positive selection of CD34(+) cells was performed in good mobilizers. The median number of cycles administered was six (4-8), and the time interval between them was 17 days. Median summation dose intensities (SDI) actually administered for the CA-TP and PE-TI protocol were 4.95 and 4.69, respectively (87% of scheduled SDI). There were 15 complete (35%) and 21 partial responses (49%), for an overall response rate of 84% (95% CI, 73%-95%). Infection or neutropenic fever occurred in 50% of the cycles. There was one treatment-related death. After a median follow-up of 26 months, the median event-free-survival was 12 months (95% CI: 10-14) and overall survival was 31 months. These high dose-intensity induction treatments seem to be feasible with sequential stem cell support.

[Intensive chemotherapy in the treatment of patients with metastatic breast cancer]. / Quimioterapia intensiva en el tratamiento de pacientes con cáncer de mama metastásico.

PURPOSE: Phase II study with intensive chemotherapy and autologous stem cells support in patients with metastatic breast cancer. METHODS: Forty-nine patients were treated with high-doses of two cytotoxic drugs and support with stem cells obtained from several leukapheresis without movilitation. The cells were reinfused forty-eight hours after finishing the administration of chemotherapy. RESULTS: Twenty-one patients (47%, CI-95%: 32.4-63.3%) achieved a complete remission. The objective responses rate was 73% (CI-95%: 57.2-85%). Overall and progression-free survival up to 4 years were 31% and 20%, respectively. Ten patients remain progression-free among 17 and 46 months. The most frequent extramedullary toxicity was hepatic and renal. Three patients (6%) died during the procedure. CONCLUSIONS: Intensive chemotherapy with hematopoietic support yields, with a moderate toxicity, a high objective response and complete remission rate. A small group of patients achieves a long progression-free survival.

Preoperative chemoradiation and adjuvant surgery in locally advanced or recurrent cervical carcinoma.

From February 1988 to May 1994, 31 patients (pts) with the established diagnosis of locally advanced (IB-IIA bulky,IIB,III,IVA) or recurrent cervical carcinoma were treated with simultaneous chemotherapy (CT) and external beam radiotherapy (RT) followed by radical surgery (RS) with or without intraoperative radiation therapy boost (IORT) to the high risk areas for recurrence. CT consisted of cisplatin 20 mg/m2 and 5-Flourouracil 1000 mg/m2 (maximum dose 1500 mg) in a 24-hour continuous IV infusion for 3-5 days during the first and fifth weeks of the scheduled course of RT. RT was delivered with standard fractionation up to a 40-46 Gy total dose. RS was performed 4-6 weeks later. Pathologic findings revealed complete and quasi-complete response (pCR+qpCR) in 74% of the surgical specimens and partial response (pPR) in 26%. With a median follow-up of 27+ months (3-71+), actuarial disease-free survival is 80% (91.3% for pCR+qpCR, 40% for pPR). Loco-regional control rate is 93.4%. The concurrent administration of RT and CT has moderate toxicity and can promote a high rate of pCR+qpCR as well as local control in high risk cervical carcinoma. The presence of a pCR or qpCR specimen seems to be correlated with good patient outcome.

High-dose BCNU and autologous progenitor cell transplantation given with intra-arterial cisplatinum and simultaneous radiotherapy in the treatment of high-grade gliomas: benefit for selected patients.

A phase II study of postoperative high-dose carmustine (HDBCNU), intracarotid cisplatin (CDDP), and radical radiotherapy in patients with high-grade glioma was performed. Patients underwent 4-6 consecutive days of blood hematopoietic progenitor cell (HPC) apheresis without prior mobilization. Chemotherapy included intracarotid CDDP, 60 mg/m2, and BCNU, 900 mg/m2. HPC were infused 48 h after HDBCNU. Whole brain irradiation, up to 50 Gy, was started on the 8th day after HPC infusion. With a median follow-up time of 44 months, median overall survival was 15.5 months. Eight patients (23.5%) are alive free of disease 2-6 years after treatment (seven out of 25 patients with glioblastoma multiforme and one out of nine patients with anaplastic astrocytoma). Survival was influenced by young age, good performance and complete surgical resection. Two patients (5.8%) died of therapy-related complications. Acute hematological toxicity of HDBCNU was moderate, with a full recovery on day 26. No acute pulmonary or hepatic toxicity was found. Late severe neurological toxicity was observed in one third of patients surviving beyond 2 years. We conclude that HDBCNU, 900 mg/m2, intracarotid CDDP and radical radiotherapy appear to benefit some patients with high-grade gliomas, and phase III studies should preferentially select young patients with resectable tumors.

Intraoperative and external preoperative radiotherapy in invasive bladder cancer: effect of neoadjuvant chemotherapy in tumor downstaging.

Absence of residual cancer (pT0) in the cystectomy specimen was evaluated in patients with invasive bladder cancer treated with intraoperative (IORT) (15 Gy) and preoperative external beam radiotherapy (EBR) (46 Gy/5 weeks) with or without neoadjuvant chemotherapy. The overall pT0 rate was 68% (67% and 70% in patients with or without neoadjuvant chemotherapy, respectively). The tolerance to the program was acceptable in both groups. It is concluded that intense, combined modality treatment is feasible in bladder cancer patients, and the addition of neoadjuvant chemotherapy does not increase the morbidity. Preliminary results on disease-free survival are encouraging.

[Complementary chemotherapy of breast cancer; experience at the University Clinic of Navarra]. / Quimioterapia complementaria del cáncer de mama; experiencia de la Clínica Universitaria de Navarra.

From 1982 to 1989, 68 patients were treated with the diagnosis of breast cancer. 57 were premenopausal and 11 postmenopausal. The most frequent stage was T2N1 (44.1%) followed by T1N1 (20.6%). The mean dosage of chemotherapy given were 91.2% for cyclophosphamide, 88% for methotrexate and 94% for 5-fluorouracil. The treatment was well tolerated and the most frequent toxicity encountered was leukopenia. The disease free survival were 89.4% at 96 month for premenopausal and 63.3% at 68 month for postmenopausal. We have not seen any differences in the disease free survival in relation to the size of the tumor or the status of the hormonal receptors of the tumor. The most important prognostic factor were the number of positive axilar nodes affected and the dosage of chemotherapy.

[Treatment of cancer of the esophagus. New strategy with the multidisciplinary treatment]. / Revisión del tratamiento del cáncer de esófago. Nueva estrategia con el tratamiento multidisciplinar.

This study is an update of the clinico-anatomical characteristics of esophageal cancer, as well as the different current therapeutic modalities, their indications and results. The therapeutic protocol for the study and treatment of epidermoid cancer of the esophages followed in the University Clinic of Navarra is likewise espounded.

120 hours simultaneous infusion of cisplatin and fluorouracil in metastatic breast cancer.

Thirty-six patients with metastatic breast cancer, 23 with documented progression of the disease after first-line chemotherapy (CAF or CMF) and 13 without prior chemotherapy, were treated with a simultaneous 120-h infusion of cisplatin (CDDP) and 5-fluorouracil (5-FU). Objective response was demonstrated in 19 patients (52.7%), stable disease in 7 patients (19.4%) and progression of the disease in 10 patients (27.7%). Similar response rate was observed according to tumor site (soft tissues, 50%; bone, 52%; lung, 63%; liver, 55%; and pleura and peritoneum, 42%) and previous treatment (previous chemotherapy, 48%; previously untreated, 61%). Median duration of response was 8 months. Toxicity was characterized by stomatitis and myelodepression and required dose adjustments in 30% of patients. CDDP and 5-FU infusion deserve further investigation because it appeared to have substantial activity in this preliminary study in metastatic breast cancer.

[Multidisciplinary protocol for the treatment of epidermoid carcinoma of the esophagus: experience from 1985 to 1989]. / Protocolo multidisciplinar de tratamiento del carcinoma epidermoide de esófago: experiencia 1985-1989.

A phase II study activated in 1985 for the multidisciplinary treatment of squamous cell carcinoma of the esophagus is described. The treatment program included simultaneous neoadjuvant continuous infusion chemotherapy with cisplatinum and 5-fluorouracil, preoperative radiotherapy (46 Gy in 5 weeks) and delayed programmed surgery (or radical irradiation in selected cases). Twenty-one patients with tumor stages I (6), II (10), III (5) entered in the study and 20 patients completed the treatment program. Severe toxicity observed was: esophagitis 100%, bone marrow aplasia 30%, severe weight loss 52%. One patient developed a tracheo-esophageal fistula at the end of radiotherapy. Clinical objective tumor response rate was 85%. Pathologic complete tumor response rate was 47%. Median follow-up of the entire group is 11 months (range 2 + to 49 + months). Ten patients have been alive for more than 12 months; six are still alive without any evidence of disease (from 12 + to 49 + months). It is concluded that the protocol described is feasible, with treatment related severe but reversible toxicities, and able to induce a high rate of tumor response and long term survivors in patients with initial locally advanced tumor stages.

Simultaneous radiotherapy and cis-platinum for the treatment of brain metastases. A pilot study.

Thirteen patients with the established diagnosis of brain metastases were treated with weekly intravenous or intra-arterial cis-platinum (40-60 mg/m2) during whole-brain irradiation (5,000 cGy over 5 weeks). Objective tumor response was observed in 12 patients (seven complete responses [CRs] and five partial responses [PRs]), and one patient showed stable disease (NC) following treatment. Chemotherapy- and radiation therapy-related toxicity was mild. There was no enhanced radiation therapy side effects on the normal tissues. Intracarotid cis-platinum with radiotherapy resulted in five CRs, two PRs, and one NC. Intravenous cis-platinum with conventional radiation therapy resulted in two CRs and three PRs. Responses according to tumor type were as follows: lung cancer (three adenocarcinoma, one mixed type, and one small-cell anaplastic carcinoma), two CRs and three PRs; breast cancer, one CR; thyroid cancer, one CR; unknown primary cancer, one CR; and melanoma, one NC. These results represent a relatively high CR rate (53.8%) for an otherwise barely manageable complication of malignant disease. Further controlled studies are recommended.