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Biomedical subjects

P F Combes

Publications and source records attributed to P F Combes.

At least 19 recordsLinked to original sources

Pharmacokinetics of teniposide (VM 26) after IV administration in serum and malignant ascites of patients with ovarian carcinoma.

Nine patients with ovarian carcinoma and malignant ascites treated with IV teniposide chemotherapy (30 mg/m2/30 min) entered this study. Plasma and peritoneal fluid levels were measured by an HPLC method with electrochemical detection. Plasma decay kinetics followed a triexponential function. A high variability of drug diffusion in ascites was noticed. Peak concentrations in ascites ranged from 1.6% to 20.5% of serum peak concentration. The concentration in peritoneal fluid reached a maximum level 6 h after the infusion ended. Teniposide was less slowly eliminated from ascites than from serum. The exposure of the inflammatory peritoneal fluid to the drug expressed by area under the concentration-time curve (AUC) was also subject to significant interindividual variation, ranging from 223 to 2332 micrograms/ml X min. However, the peritoneal AUC was correlated with serum AUC and with the systemic clearance of the drug. A significant relationship between gamma glutamyltranspeptidase and both systemic clearance and either the serum or the peritoneal AUC was found, suggesting that liver plays a role in drug disposition.

Aged↗

Results of radiotherapy alone in 581 patients with Stage II carcinoma of the uterine cervix.

From January 1976 to December 1978, 581 previously untreated patients with Stage II carcinoma of the uterine cervix were treated by radiotherapy alone in nine departments of radiotherapy in France. This retrospective analysis was undertaken in an attempt to evaluate the therapeutic results and prognostically significant factors. The initial clinical staging and the therapeutic guidelines were as outlined at the U.T. M. D. Anderson Hospital in Houston; all our patients were treated by standardized protocols combining external beam irradiation and intracavitary irradiation with cesium sources. The overall locoregional control rate was 83.2%, with total disease control of 74.5%. Uncorrected actuarial survival rates are 76% at 3 years and 68% at 5 years. The incidence of severe posttherapeutic complications is 7.2%. Clinical substaging, patient's age at the time of the diagnosis, lymphangiogram findings, and tolerance to external irradiation were all found to have prognostic significance. According to those findings, the possibilities of improving the results are discussed.

Actuarial Analysis↗

Exhausted platelets in patients with malignant solid tumors without evidence of active consumption coagulopathy.

Twenty-four patients with various types of tumors and without evidence of consumption coagulopathy (normal routine coagulation tests) were investigated for intraplatelet ATP, ADP, serotonin, beta-thromboglobulin and platelet factor 4; the percentage of light circulating platelets was also determined. Evidence for an acquired storage pool defect was found in seven patients (29%) without any correlation with the clinical status, the presence of metastases, platelet count or fibrinogen level. These results show that exhausted platelets are commonly encountered in cancerous patients even in the absence of consumption coagulopathy. The precise mechanism of this abnormality remains to be established.

Adenosine Diphosphate↗

Results of the treatment of 165 lid carcinomas by iridium wire implant.

A group of 160 adult patients with epithelial tumors of the lid and/or canthi treated by iridium 192 wire implant are presented. There were 165 epithelial tumors, most of them were basocellular type (85%). In all cases, a nonradioactive procedure was used with disposable angiocatheters before introducing active wires. Respectively, 111/114 (97.4%) of "new" lesions and 48/51 (94%) of previously treated tumors were definitively cured by iridium wire implant. Among the 6 local recurrences, 4 were salvaged by a second iridium implant, and the two others by extensive surgery. Local side effects were present in 30 patients (18%): impairment of the eyelid aperture 9, stenosis of lacrymal ducts 7, eversion of the lid 7, lack of substance 7. These postherapeutic complications were significantly more frequent in treating recurrent lesions (15/48, 31.2%) than in previously untreated tumors (15/112, 13.4%). No visual complication was observed even in the early patients of this series.

Adenocarcinoma↗

[Carcinoma of the nasopharynx. Clinical signs and therapeutic problems].

Most of the carcinoma of the nasopharynx diagnosed in our country, are loco-regionally advanced disease. Thus 31/54 (57%) of our patients referred to the Centre Claudius Regaud between 1970 and 1980 were T2 N3, T3 N3, T4 N0 or N1 N2 N3. In spite of this poor initial presentation external radiotherapy can achieve a quite good rate of tumoral control inside the treated volume. In our series there were 17/47 (36%) tumoral and/or nodal recurrences and 7/47 (15%) metastases without local or regional failure. Improvement of initial évaluation of the tumoral volume is now obtained by the systematic use of C.A.T. and this procedure should reduce local failure rate. In the other hand, the association of chemotherapy and radiotherapy should be useful in treating advanced disease or poorly differentiated carcinomas with high metastatic risk.

Adolescent↗

[Cancer of the rectum: preoperative radiotherapy (344 cases)].

Radiation therapy prescribed as an adjuvant to surgery is an effective treatment of many cancers but has not been universally accepted for treatment of rectal cancer. Since 1969, preoperative radiation therapy of rectal carcinoma has been proposed in a curative intent, both at Centre Paul Lamarque in Montpellier and at Centre Claudius Regaud in Toulouse, France. Megavoltage radiotherapy was used in all patients and doses ranges from 35 to 40 Gy during 2.5 to 3 weeks. Among the 344 patients treated between 1969 and 1981, the ratio of abdominoperineal excision to anterior resection was 239/105, the percentage of pelvic recurrence was 7,8 per cent, and the 5-year survival rate, including postoperative mortality (5.2%) was 78 per cent in the Centre Claudius Regaud series and 64 per cent in the Centre Paul Lamarque series. The 10-year survival rate was 50 per cent. There was no evidence of an increased morbidity following irradiation. Pathologic staging showed no residual tumour in the excised specimen in 5.2 per cent of the cases. The number of Dukes'C cases was smaller than according to the clinical pre-treatment assessment of the tumours (16%). Ultrasonography of the liver and plasmatic CEA determination avoid irradiation of metastatic patients. Further development of this curative approach should include a postoperative boost of 25 Gy for patients who are at high risk for local failure in the pelvis, and an adjuvant chemotherapy for Dukes'C patients.

Aged↗

Postoperative irradiation of carcinoma of the head of the pancreas area: short-time tolerance and results to precision high-dose technique in 18 patients.

During the period from January 1977-August 1979, 18 patients with biopsy-proven pancreas duct or ampullary adenocarcinoma with no distant or liver metastases underwent external beam radiation therapy following laparotomy. With the use of a 25 MEV photon beam and a four field "box" technique, the dose delivered to the target volume identified with radio-opaque clips at laparotomy was 6000 rad in six weeks, while largely sparing the spinal cord, kidney, liver and gut. All patients subjected to low fat, gluten free diet completed treatment as planned without any acute reaction. Three patients developed delayed pancreatic insufficiency. According to actuarial survival analysis and low morbidity such an approach may lead to increase survival in patients with pancreatic cancer.

Adenocarcinoma↗

[Primary tumors of the renal pelvis and ureter: value of postoperative external radiotherapy (author's transl)].

Twenty-four observations of primary malignant tumors of the renal pelvis and ureter derived from epithelial cells were included in this study. Thirteen patients were treated by radiotherapy and surgery. In eleven patients, surgical excision was the only treatment. Although patients were not randomized there was no significant difference between the two groups concerning the following parameters: age distribution, sex ratio, stage of disease, histological grade, surgical procedure. The morbidity related to external radiotherapy (megavoltage technique, delivering 45 grays in 5 weeks) was low: only one patient developed retroperitoneal fibrosis. No patient was lost to follow-up. Local recurrence occurred in 54.5% of the patients treated by surgery alone, against 15.5% after combined radio-surgical therapy. The overall three-year survival rate was 35% without any significant difference between the two groups. The authors advocate postoperative high-voltage radiotherapy for non-disseminated carcinoma of the renal pelvis and ureter.

Adult↗

Treatment of carcinoma of the penis by iridium 192 wire implant.

Since 1971, a group of 22 adult patients with squamous cell carcinoma of the penis have been treated by iridium 192 wires implant. There were 6 T1 tumors, 14 T2 tumors and 2 T3; only one patient (T3) presented with local failure after implant. Local necrosis occurred in 2 patients without local tumoral recurrence, but was sufficient enough to warrant amputation. Thus 19/22 (86%) patients were locally cured with penile conservation. In these patients the most frequent post-therapeutic complication is chronic urethral stenosis (9/19 patients, 47%) requiring repeated instrumental dilations. Four patients presented with initial inguinal metastatic nodes; only one was cured by radiosurgical treatment. Among patients without metastatic nodes at the time of diagnosis, none had delayed metastatic nodes. Three patients died of nodal evolution, 5 patients died of intercurrent disease without evidence of disease and 14 are now alive and NED. It appears that iridium 192 wires implant is the most effective conservative treatment of invasive squamous cell carcinoma of the penis; however, these results confirm that no particular treatment is required for inguinal nodal areas for patients who initially present with no disease.

Adult↗

[Epidermoid epitheliomas of the upper respiratory and digestive pathways in females].

Ninety-five females with squamous cell carcinoma of the head and neck are reported. Tobacco and alcohol habits were present in only 18% of patients; in these cases tumoral behavior and prognosis are quite similar to those of male patients. When no particular epidemiology was found, female patients present special tumoral localizations as gum, cheek or palate. In addition these patients are elderly, mean age above 75 years. Radiotherapeutic management of female patients allow the same results than in treating males; consequently, since female patients are more elderly than males, these therapeutic results advocate aggressive therapy even in female patients above 80 years old.

Aged↗

[Cerebral irradiation as adjuvant therapy in the treatment of small cell carcinoma of the lung (author's transl)].

The authors present the results of a non randomized study of 33 patients suffering from small cell carcinoma of the lung. After a similar course of monthly chemo-therapy (Endoxan Oncovin, Natulan, CCNU) and mediastinal irradiation in a dose of 30 grays in 10 fractions over two weeks, 14 patients were given adjuvant cerebral irradiation, the 19 others made up the control group (30 grays to the brain overall in 10 fractions over two weeks). With a minimum follow up for 12 months, 42% of the control group had evidence of cerebral secondaries, as opposed to none in the irradiated group with any neurological signs whatsoever. The indisputable efficacy of adjuvant cerebral irradiation contrasts with the absence of any significant improvement in survival time : 2 patients are alive and in complete remission, 1 in each group, while the mean survival was 12.3 and 11.7 months respectively. This is explained by the continued occurrence of extra-cerebral metastatic deposits such as the liver or mediastinum where the efficacy of systemic therapy remains uncertain. The therapeutic approach is currently orientated in two directions : - to raise the dose delivered to the mediastinum even if it appears radiologically normal. - to continue research into new chemo-therapeutic combinations more specifically active at the hepatic level.

Antineoplastic Agents↗