Nonsurgical approach in stage I and stage II breast cancer.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
D Khayat
Publications and source records attributed to D Khayat.
[Pancreatic endocrine tumor with metastases and increase of alpha-fetoprotein. A case report].
The authors report the case of a 48 years old man presenting a pancreatic islet cell carcinoma (gastrinoma) with liver, nodes and peritoneal metastases, associated with an elevated alpha-fetoprotein (AFP) concentration. Incomplete remission was first obtained with a chemotherapy using Streptozotocin combined with 5-Fluorouracil, in association with a Somatostatin analogue (SMS 201-995). But when relapses occur, another chemotherapy was not so effective. Serum gastrin and AFP levels had the same evolution and appear to have the same interest to follow the course of the disease.
Antineoplastic Combined Chemotherapy Protocols↗
[Treatment of experimental liver tumors by in vivo suicide gene transfer in rats].
We investigated whether the transduction of a suicide gene might induce the elimination of malignant solid tumours. BDIX male rats were given an intra-hepatic injection of a mixture containing DHDK12 tumor cells and xenogeneic fibroblasts. The latter were producing either the herpes simplex virus type 1 thymidine kinase HSV1-TK- or nls-lac Z(control)-expressing recombinant retroviral particles. 5 days later, a time at which the tumor is macroscopic, all the rats were treated with ganciclovir, a nucleoside analog that is metabolized by HSV1-TK into a toxic compound. After 5 days of treatment, a dramatic reduction in tumour volume was noted in the HSV1-TK group. These results delineate a new therapeutical strategy for the treatment of disseminated liver metastases or of a large variety of solid malignant tumours.
Animals↗
[Primary chemotherapy in the treatment of breast cancer].
Between 1980 and 1992, 457 consecutive patients with initial breast cancer entered two successive protocols combining neoadjuvant chemotherapy, hormonotherapy (tamoxifen) and locoregional radiotherapy (teleradiotherapy and boost by iridium) as exclusive locoregional treatment. Cytological diagnosis, hormone receptors, cytological grading were provided by fine needle aspiration. Both protocols included velbe, thiotepa, methotrexate, 5FU and adriamycin with some minor differences regarding the schedule of doses and their number during induction and during the consolidation phase. In both studies, over 50% patients had locally advanced breast cancer (IIb, IIIa or IIIb). Chemotherapy induced tumor regression over 50% in 91% patients of the first protocol (30% complete clinical remission CR) and in 94% patients of the 2nd protocol (40% CR): in this protocol 20 poor responders were given a rescue protocol (2 CR; 9 partial remissions). The 5 year actuarial rate of breast preservation is 94% and the 5 year actuarial rate of local relapses is 15%. The cosmetic results according to Danoff are excellent 20%, good 55%, mean 35%. Disease free survival and overall survival compare favorably to published data: they depend on TNM stages, tumor differentiation and chemotherapy induced early tumor regression.
Adult↗
Fotemustine: an overview of its clinical activity in disseminated malignant melanoma.
Fotemustine is a new chloronitrosourea which is active against disseminated malignant melanoma (DMM), and especially against cerebral metastases (CM). This efficacy has been widely demonstrated through many phase II studies. A multicentre trial of monotherapy was undertaken in 153 evaluable French patients. A response rate (RR) of 24.2% (25.0% RR in CM; 31.8% in non-visceral metastases (NVM) was obtained. Three other phase II studies confirmed these results with respective objective RR of 16.7%, 20.0% and 47.0% and RR in CM of 8.3%, 14.3% and 60.0%. Fotemustine has also been used in combination with dacarbazine (DTIC), in patients with DMM. The RR among 103 patients was 27.2% (26.3% in CM, 37.5% in NVM), confirming the activity of fotemustine. The two drugs have also been administered sequentially, in order to exploit their synergism in interfering with the O6 alkyltransferase. Impressive RR have been achieved, especially in patients with visceral metastases (VM) but at the expense of a pulmonary toxicity that does not arise with other treatment schedules and which precludes its use outside of strictly conducted clinical trials.
Antineoplastic Combined Chemotherapy Protocols↗
[To plead for the introduction of a new psycho-oncology in France].
Psycho-oncology is a new discipline which considers the problem of psychological distress of cancer patients in a different manner to that of classical psychoanalysis. It is symptomatic, practical, scientific, and widely used on an international scale. It provides fresh clarification and the latest practical techniques in many areas: treatment of side-effects subsequent to radio- or chemotherapy, problems connected with life "after", risk factors, psychosocial interventions for normal stress reactions, treatment of anxiety and depressive syndromes, etc. This approach has been adopted to only a limited extent in France and deserves wider diffusion.
Combined Modality Therapy↗
[Value of chemotherapy preceding exclusive conservative loco-regional radiotherapy in breast cancer].
Explore the source record for details and available documents.
Antineoplastic Combined Chemotherapy Protocols↗
MRI of liver tumors using gadolinium-DOTA: prospective study comparing spin-echo long TR-te sequence and CT.
Thirty-nine patients with liver tumors were examined using MRI at 0.5 T before and after intravenous bolus injection of either 0.1 mmol/kg (n = 18) or 0.2 mmol/kg (n = 21) of Gadolinium-Dota, using spin-echo T1-and T2-weighted sequences before injections and spin-echo or gradient-echo sequences after injection. When contrast-to-noise (C/N) data were normalized relative to time, optimal mean C/N was observed after gadolinium injection. However, subjective study and case-by-case C/N measurement showed better contrast for SE 2000/60 and CT with injection in 62% and 42% of cases, respectively.
Adult↗
Fotemustine (S 10036) in the intra-arterial treatment of liver metastasis from malignant melanoma. A phase II Study.
Fotemustine is a new nitrosourea which has shown some efficacy on disseminated malignant melanoma (DMM) (24.2% response rate (RR) among 153 patients in a Phase II trial) but little activity on hepatic metastasis (8.8% RR). In order to improve those poor results, hepatic intra-arterial infusion (HIAI) of fotemustine was performed. After two years, thirteen patients, all in good general condition, were evaluable. Seven were pretreated and six had extrahepatic metastasis on entry into the study. All patients had a surgically implanted intra-arterial catheter. The induction cycle consisted of 100 mg/m2/week for 3-4 weeks, followed by 5 weeks rest and maintenance therapy of 100 mg/m2 every 3 weeks for stabilized or responding patients. Two complete responses (CR) (72+ and 145+ weeks) and six partial responses (PR) (7-18.5 weeks) were observed. The hepatic RR reached 61.5%. A RR of 42.8% was registered on preexisting EHM (one CR and one PR on cerebral lesions). Nevertheless, this treatment is limited by the high progression rate of 46.1% in extrahepatic disease. Toxicity was mainly hematologic (grade III-IV), comprising 36% neutropenia and 15% thrombopenia. Hepatic intra-arterial infusion of fotemustine is efficient therapy for liver metastases of DMM, but combination schedules (IV + HIA) are warranted.
Adult↗
Neoadjuvant chemotherapy.
Explore the source record for details and available documents.
Antineoplastic Agents↗
[Tumor regression as a prognostic factor in breast cancer].
Two hundred and fifty evaluable patients with breast cancer entered a protocol combining neoadjuvant and consolidation therapy by vinblastine (V), thiotepa (T), methotrexate (m) and 5-fluorouracil (f) (VTMF) with or without Adriamycin (A) (Doxorubicin; Adria Laboratories, Colombus, OH USA), and radiation therapy as exclusive locoregional treatment. Tamoxifen was given to 195 patients, 130 post menopausal and 65 pre-menopausal, and was omitted in 55 patients (31 postmenopausal and 24 pre-menopausal). There were 19 stage I, 86 IIa, 51 IIB, 36 IIIA and 58 IIIB. Primary chemotherapy induced tumor volume regression of more than 75% in 41% of the patients and complete clinical regression in 30% of the patients. The 5 years DFS rates were 100% for stage I, 82% for stage IIA, 61% for stage IIB, 46% for stage IIIA and 52% for stage IIIB patients. Among the 72 primary relapses there were 39 distant metastases, 6 locoregional and distant metastasis and 27 isolated locoregional metastases. The actuarial rate of locoregional recurrence is 13% for T2, 18% for T3, 19% for T4. At 5 years the rate of breast preservation was 94%. Cosmetic results are excellent or good for most patients. The 5 years overall survival (OS) were 95% for stage I, 94% for stage IA, 80% for stage IIB, 60% for stage IIIA and 58% for stage IIIB. In multivariate analysis tumor regression appears as an independent and significant factor. This parameter should be preserved in many patients with infiltrative breast cancer.
Actuarial Analysis↗
[Fotemustine: a pilot phase II trial in sarcoma of the soft tissues].
Fotemustine has been administered to 10 patients with metastatic or redux soft sarcoma in a phase II pilot study. The main inclusion criteria were: at least one measurable site, Karnofsky index (KI) higher than 60%, no specific treatment within the last 4 weeks, correct haematological status. Induction treatment comprised fotemustine 100 mg/m2 D1-D8-D15 in a 1 h intravenous infusion protected from light, followed by a 5-week rest period. In patients with no progressive disease, maintenance treatment comprised fotemustine 100 mg/m2 D1 q 3 weeks, until progression or toxicity. Patients characteristics were: 9 M/1 F; median age: 51 years [26-66]; median KI 90% [60-100]; median number of previous drugs: 5 [2-8]; 6 patients had two or more metastatic sites and one patient had developed a sarcoma following chest radiotherapy. Evaluation was carried out in weeks 4 and 8, following the first fotemustine injection. One case of minor response and one case of stabilisation were observed, but they were of short duration. The main toxicity was haematological with delayed leucopenia and thrombopenia (nadir: week 6). In patients who have undergone previous chemotherapy, fotemustine is not efficient according to the first step of the Gehan statistical guidelines.
Adult↗
[Professor Claude Jacquillat (1929-1990)].
Explore the source record for details and available documents.
France↗
Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases.
One hundred sixty-nine patients with histologic evidence of disseminated malignant melanoma, including patients with cerebral metastases, were entered into a Phase II study of the nitrosourea fotemustine. The treatment regimen consisted of a 100 mg/m2 1 hour IV infusion every week for 3 consecutive weeks, followed by a 4- to 5-week rest period (induction therapy). In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 every 3 weeks until the disease progressed. One hundred fifty-three patients were evaluable for response. Three complete responses and 34 partial responses were observed (according to the World Health Organization criteria), leading to an objective response rate of 24.2% (95% confidence interval: 17.4% to 31.0%). Responses were also documented on cerebral (25.0%), visceral (19.2%), or nonvisceral (31.8%) metastatic sites. The median duration of response was 22 weeks (range, 7 to 80 weeks). The objective response rate in previously untreated patients was 30.7% (19 of 62 patients). The main toxicity was hematologic with delayed and reversible leukopenia and/or thrombopenia. The objective response rate observed (especially in untreated patients), the activity on cerebral metastases, and the small amount of extra-hematologic toxicity encountered suggest that fotemustine is an effective drug in disseminated malignant melanoma.
Adult↗
Chemotherapy by fotemustine in cerebral metastases of disseminated malignant melanoma.
A total of 42 patients with cerebral metastases of malignant melanoma were included in this study of the nitrosourea fotemustine. The treatment plan consisted of a l-h i.v. infusion of 100 mg/m2 fotemustine every week for 3-4 weeks, followed by a 4- to 5-week rest period. Responding or stabilised patients then received 100 mg/m2 fotemustine every 3 weeks. Among the 39 evaluable patients, 2 complete responses and 9 partial responses were documented, leading to an overall response rate of 28.2%. Most of the responses were obtained in previously untreated patients and/or those presenting with a single cerebral metastasis. Toxicity was mild and mainly hematological, especially in patients previously treated by polychemotherapeutic regimen. Our study confirms the activity of fotemustine in cerebral metastases of disseminated malignant melanoma.
Adult↗
Renal effects of S10036 in man.
The renal hemodynamic and tubular effects of S10036 (fotemustine) were evaluated in seven patients with advanced malignancy. Initial evaluation carried out prior to treatment and repeated 1 day after the first fotemustine infusion and 7 days after the second included clinical, haematological parameters, liver-function tests, and determination of the glomerular filtration rate, renal blood flow and enzymuria. The glomerular filtration rate was 108 +/- 3.7 ml/min before treatment and remained stable after the first (117 +/- 5 ml/min) and second (124 +/- 6 ml/min) fotemustine infusions. Renal blood flow and urinary beta 2-microglobulin and N'-acetylglucosaminidase excretion were also not modified by fotemustine administration. We conclude that fotemustine does not acutely alter renal haemodynamics, nor does it have direct tubular toxicity.
Acetylglucosaminidase↗
Changes of soluble CD16 levels in serum of HIV-infected patients: correlation with clinical and biologic prognostic factors.
The modulation of soluble CD16 titers in human immunodeficiency virus (HIV)-infected patients' serum, with an initial increase in Centers for Disease Control (CDC) clinical stage II and III patients followed by a dramatic drop in patients with AIDS (CDC clinical stage IV), is reported. These changes are statistically correlated with the CDC staging system, the number of CD4+ cells, the amount of p24 antigen in serum, and the anti-p24 antibody titers, indicating the potential value of soluble CD16 titer as an easily available serum marker of disease progression. To evaluate a possible link between this observation and the expression of membrane-associated CD16/FcRIII, flow cytometry immunofluorescence analysis was performed on peripheral blood lymphocytes from patients in three CDC stages; no specific changes in the number of natural killer cells expressing CD16+ antigens or in the total number of Leu19+ cells were found. However, there was a statistical correlation between the absolute number of T cells expressing CD16 antigens (CD3+/CD16+) and the modulated titers of soluble CD16 in HIV-infected serum.
Adult↗
Functional and metabolic activity of polymorphonuclear leukocytes from patients with adult respiratory distress syndrome: results of a randomized double-blind placebo-controlled study on the activity of prostaglandin E1.
Indirect and experimental evidence suggests that polymorphonuclear leukocytes, responding to an activating signal presumably related to the complement cascade activation, are involved in the pathogenesis of the adult respiratory distress syndrome (ARDS). The pathologic changes seem to be result of the polymorphonuclear leukocyte margination within the pulmonary capillary vessels and their activation with subsequent release of vasoactive peptides (thromboxane A2, prostaglandin E2) and toxic intracellular compounds. This study confirms that adherence, chemotaxis, and chemiluminescence are increased in polymorphonuclear leukocytes from patients with ARDS. Enhanced chemotactic and chemiluminescence capacities are likely specific to ARDS, whereas increased polymorphonuclear leukocyte adherence seems to be nonspecific. If increased polymorphonuclear leukocyte activation is important in the pathogenesis of ARDS, the inhibition of this phenomenon could play a therapeutic role. This double-blind prospective study was undertaken to assess if polymorphonuclear leukocyte activity is inhibited in vivo by the iv administration of prostaglandin E1 (PGE1) in patients with ARDS. A continuous infusion of PGE1 at a dose of 30 ng.kg-1.min-1 for 7 days did not modify the functional activity of polymorphonuclear leukocytes in patients with ARDS. Because hemodynamic instability was seen during infusion of this dose of PGE1, an increased dose was not tested. At the dose of PGE1 tested, no significant effect upon the function activity of polymorphonuclear leukocytes in patients with ARDS could be demonstrated.
Adult↗