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J Gligorov

Publications and source records attributed to J Gligorov.

16 recordsLinked to original sources
PubMed2006

Phase I study of high-dose topotecan with haematopoietic stem cell support in the treatment of ovarian carcinomas: the ITOV 01 protocol.

Topotecan has demonstrated activity in ovarian carcinomas. In order to increase the tumour response rate and to define the maximum tolerated dose (MTD) of topotecan, we decided to develop a high-dose phase I regimen supported by stem cell support. High-doses schedules using a 1-day single administration have MTDs of 10.5 (24 h continuous infusion (CI)) or 22.5 mg/m2 (30 min infusion). Five-day CI induces grade IV mucositis at high doses (MTD<12 mg/m2). We chose to administer topotecan in a 5-day schedule with a 30 min daily infusion. Patients were scheduled to receive one cycle of therapy. The first dose level was 4.0 mg/m2/day x 5 days. Limiting toxicities were defined as toxic death, grade IV non-haematopoietic or haematopoietic toxicity >6 weeks. From August 1998 to April 2002, 49 patients were included. Forty-three patients have completed one course and 15 have received two cycles. One patient treated at level 7 mg/m2/day died of sepsis. Median duration of grade IV neutropenia was 9 days. Two episodes of grade IV diarrhoea were observed at level 9.5 mg/m2/day. Pharmacokinetic data were linear within the dose range of 4-9.0 mg/m2/day. The MTD was reached at 9 mg/m2/day x 5 days.

Adolescent↗
PubMed2005

[The use of GnRH analogues in early and advanced breast carcinomas].

Breast cancer is often an estrogen-dependent disease. The primary goals of the treatment of breast carcinomas are multiple, depending on the situation in which the patients are treated. In adjuvant setting, the aims are to delete the time of relapse, to increase the overall survival, and to offer to the patients the best quality of life they may expect. Tamoxifen is the standard hormonal agent for premenopausal women with receptor-positive breast cancer. Recent data show an increasing role for aromatase inhibitors in postmenopausal women. In metastatic setting, the primary goals are improved quality of life and prolonged survival; effective therapies with minimal toxicity, such as endocrine therapy, are highly desirable and should be considered a primary option over chemotherapy for selected estrogen-receptor positive patients. Ovarian ablation has been worldwide used. Methods of irreversible ovarian ablation include surgical oophorectomy and ovarian irradiation. Potentially reversible castration can be medically accomplished using luteinizing hormone releasing hormone analogues (LHRH agonists). In the metastatic setting, ovarian ablation (induced by the use of LHRH agonists or by surgical ovarian ablation) and tamoxifen monotherapies produce comparable outcomes, and may be more effective when used together (combined estrogen blockade). In advanced breast cancer, the combination prolongs the progression-free survival and increases response rates and duration of response rate relative to the use of LHRH agonist alone. In the adjuvant setting, data suggest that ovarian ablation followed by tamoxifen produces similar results to those obtained with adjuvant chemotherapy in hormone-receptor positive breast cancer women. The value of combining these modalities remains unclear, but the addition of the LHRH analogue goserelin to standard treatment results in a significant benefit in terms of relapse-free and overall survival, especially for estrogen-receptor positive patients. Finally, considering the efficacy of the new aromatase inhibitors, the interest of combining these drugs with the LHRH analogues has yet to be defined, both for pre- and post-menopausal patients.

Aromatase Inhibitors↗
PubMed2005

Sequential high-dose chemotherapy protocol for relapsed poor prognosis germ cell tumors combining two mobilization and cytoreductive treatments followed by three high-dose chemotherapy regimens supported by autologous stem cell transplantation. Results of the phase II multicentric TAXIF trial.

BACKGROUND: High-dose chemotherapy (HD-CT) is able to circumvent platinum resistance of resistant/refractory germ-cell tumors (GCTs), but expectancy of cure remains low. New strategies are needed with new drugs and a sequential approach. MATERIALS AND METHODS: Patients with relapsed poor-prognosis GCTs were scheduled to receive two cycles combining epirubicin and paclitaxel (Taxol) followed by three consecutive HD-CT supported by stem cell transplantation [one course combining cyclophosphamide, 3 g/m(2) + thiotepa, 400 mg/m(2), followed by two ICE regimens (ifosfamide, 10 g/m(2), carboplatin, AUC 20, etoposide, 1500 mg/m(2))]. RESULTS: From March 1998 to September 2001 (median follow-up, 31.8 months), 45 patients (median age, 28 years) were enrolled in this phase II study. Twenty-two patients received the complete course. Twenty-five patients died from progression and five from toxicity. The overall response rate was 37.7%, including an 8.9% complete response rate. The median overall survival was 11.8 months. The 3-year survival and progression-free survival rate was 23.5%. The 'Beyer' prognostic score predicted the outcome after HD-CT. CONCLUSION: Although our results warrant further studies on HD-CT in relapsed poor prognosis GCTs, patients with a Beyer score >2 did not benefit from this approach and should not be enrolled in HD-CT trials. Better selection criteria have to be fulfilled in forthcoming studies.

Adolescent↗
PubMed2000

Mechanisms of action of bisphosphonates on tumor cells and prospects for use in the treatment of malignant osteolysis.

Malignant osteolysis is a common complication of many cancers, most notably breast cancer, prostate cancer, and multiple myeloma. Hypercalcemia, pain, and fractures are the main manifestations. Malignant osteolysis can be fatal or cause a rapid deterioration in quality of life. The underlying mechanism in tumor cem-mediated activation of osteoclasts, whose function is normally to resorb bone. It follows that pharmacological agents capable of inhibiting osteoclast activity, including bisphosphonates, are likely to be useful in the treatment of malignant osteolysis. Also, experimental evidence suggest that bisphosphonates act on the tumor cells themselves, either by inhibiting mechanisms involved in the development of bone metastasis (tumor invasion, adhesion of tumor cells to the bone matrix) or by inducing apoptosis of tumor cells. Many clinical trials have found bisphophonates to be effective in the treatment of complications due to malignant osteolysis. Based on these studies, bisphosphonates are now indicated to treat hypercalcemia and to prevent skeletal complications of metastatic breast cancer and myeloma, in a dosage of 1600 mg.d orally for clodronate or 90 mg every four weeks intravenously for pamidronate. Osteoclast inhibition is clearly the mechanism underlying the efficacy of bisphosphonates in these clinical trials. Recent clinical trials found that prophylactic bisphosphonates therapy in patients with nonmetastasic breast cancer decreased the incidence of bone metastases, thus supporting a direct effect of biphosphonates on tumor cells. However, conflicting experimental and clinical data have been reported, so that it remains uncertain whether bisphosphonates have anti-tumor effects in vivo in humans. Nevertheless, biphosphonates now have an undisputed place in the therapeutic armamentarium for cancer.

Animals↗
PubMed1999

[Small cell lung carcinoma].

Small cell lung carcinoma represents less than twenty five percent of all lung cancers. Nevertheless, a lot of studies permitted to better define this cancer and to propose specific therapeutic approaches. Clinical symptoms, results and roles of chemotherapy, radiation therapy and surgery are discussed in this review.

Antineoplastic Agents↗
PubMed1998

[Adenocarcinoma of the pancreas. General characteristics].

EPIDEMIOLOGY: Pancreatic carcinoma ranks fifth among the leading causes of cancer death in developed countries. Although the incidence of pancreatic cancer is about 10 per 100,000 inhabitants, the five-year overall survival is barely one to 4%. Few risk factors have been identified. Smoking increases the relative risk by 1.5, chronic pancreatitis by 26. Hereditary formes are rare. PATHOLOGY AND MOLECULAR ABNORMALITIES: Adenocarcinomas of the ductal phenotype represents about 90% of the pancreatic tumors. Seventy percent of adenocarcinomas are located in the head. Mutations of K-ras oncogene and p53 anti-oncogene are noted, respectively, in 80 to 90% and 70% of the ductal adenocarcinomas. The mutation of p53 is associated with a poor prognosis. Certain less frequent forms such as mucinous cystadenocarcinomas, or intraductal papillary-mucinous tumors seem to have a better prognosis. However, this is not true for acinar cell carcinomas responsible for various paraneoplastic syndromes. PATTERN OF SPREAD: The disease arises in the ductal epithelium and rapidly spreads to regional lymph nodes and the liver. At diagnosis, nodal involvement is found in 80% of cases. Half of the patients have detectable visceral metastasis with a median survival of three to six months. Among the remaining non metastatic patients, approximately one in 5 has undetected peritonal carcinomatosis. Only 10 to 20% of the patients undergo surgical complete resection with a median survival of 15 to 19 months.

Adenocarcinoma↗
PubMed1998

[Adenocarcinoma of the pancreas. Diagnosis and evaluation].

SYMPTOMS: Pain, jaundice, or weight loss are the presenting features of 90% of the cases. Patients with tumors of the body or the tail of the pancreas do not rapidly develop jaundice. Therefore, their diagnosis is delayed and metastasis are more frequently detected at diagnosis. RADIOLOGIC DIAGNOSIS: The diagnosis may be established by ultrasonography, endoscopic ultrasonography and most importantly by CT scan with helicoidal continuous acquisition and contrast injection. However, these methods do not efficiently detect tumors smaller than 2 cm or with only superficial peritoneal involvement. Laparoscopy and angiography are used less and less frequently to evaluate resectability. The diagnostic work-up with CT scanning is able to anticipate resectability in 50 to 90% of the cases. PATHOLOGY: Histopathology must be obtained since 10% of the pancreatic carcinoma are not of the ductal type and not all pancreatic tumors are malignant. When a pathological specimen cannot be obtained during surgery, a cytology specimen may be obtained with a fine needle guided by CT scan. PROGNOSIS: Survival depends on the possibility of a complete resection of the tumor. If complete resection is obtained, the prognostic factors are in decreasing importance: tumor size, lymphatic and vascular involvement, and invasion of peri-pancreatic tissues.

Adenocarcinoma↗
PubMed1996

[High-dose therapy and hematopoietic cell autotransplantation in the treatment of adult gynecologic tumors].

Autologous bone marrow transplantation for the treatment of gynecologic tumors in adults remains an uncommon therapeutic approach. The feasibility of such high-dose therapies is clearly proved, especially with the advent of hematopoietic growth factors and the rescue by the peripheral stem cells to reduce the duration of the chemotherapy-induced myeloid aplasia. The question is to exactly define the place of high-dose therapy in the land of solid tumors. In the treatment of poor prognosis breast cancer, high-dose therapy with autologous bone marrow transplantation or with peripheral stem cells support is able to convert some patients with partial response into complete responders. However, the consequences on overall survival and disease-free survival are not convincing. For metastatic breast cancer and for poor-prognosis tumors (inflammatory breast cancer, axillary metastatic nodes > or = 8), the interest of high-dose therapy has to be determined by randomized studies. These studies are ongoing in USA and in France. For the treatment of poor-prognosis ovarian cancer, the situation is more difficult to appraise. Randomized studies have to be done to precisely define the interest of high-dose therapy in terms of response and disease-free survival for the treatment of ovarian carcinomas.

Adult↗