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Biomedical subjects

P Bastit

Publications and source records attributed to P Bastit.

At least 37 records · Page 2Linked to original sources

[Phase II trial as 2nd line chemotherapy with 5 fluorouracil and cisplatin (5FU-CDDP) for advanced breast cancer].

Thirty patients with advanced breast cancer, previously treated with anthracycline and 5 fluorouracil in bolus administration, were evaluated with a chemotherapy regimen generally used in head and neck cancer. Treatment schedule consisted of: cisplatin 100 mg/m2 on d 1 and 5 fluorouracil 1000 mg/m2 continuous infusion on d 2-3-4-5 every 21 d. With all measurable lesions and 27 evaluable patients, the response rate was 29% (95% confidence interval: 12-47%), with 5 complete responses (3 soft tissue - 2 lung) and 3 partial responses (1 lung - 2 liver). The median duration of response is 4.5 months (range 2-11 months). The 30 patients (93 courses) are evaluable for toxicity. Hematologic toxicity was mild: anemia 68% grade 0, neutropenia 68% grade 0 and thrombocytopenia 83% grade 0. Nausea and vomiting were severe 83% grade 3 + 4 at d 1. Others side effects were mild including 5/91 mucositis grade 2 + 3, peripheral neuropathy 1/31 grade 2 and 2/91 reversible rise in serum creatinine greater than 1.5 mg/dl.

Adult↗

Phase II study of epirubicin in advanced soft tissue sarcoma.

Thirty-seven patients (pts) with previously untreated and measurable advanced soft tissue sarcoma entered this phase II study: 22 men and 15 women were included. Median age was 58 (range: 20-71). The starting dose of epirubicin was 100 mg/m2 IV bolus every 3 wks. In the case of minimal myelosuppression, the dose was increased by 10 mg/m2 to 130 mg/m2 (Mean dose per cycle: 105 mg/m2). Median cumulative dose of epirubicin administered was 445 mg/m2 (range: 200-1320 mg/m2). From 32 evaluable pts, one had a complete response (CR), 5 a partial response (PR), (CR + PR = 18.7% +/- 13.8%), 12 showed no change (37.5%) and 14 had progressive disease. The number of complete or partial responses observed was not modified by increasing the doses of epirubicin. Median time to progression was 4 months. From 32 pts evaluable for toxicity, hematologic toxicity at d 21 was mild. Non hematological toxicities consisted of nausea and vomiting in 74% of pts (WHO grade 3 = 5%), stomatitis in 12.2% (WHO grade 3 = 3%) and alopecia in 91% (WHO grade 2-3 = 72%). No cardiac dysfunction was recorded during the treatment, even though 7 patients received more than 800 mg/m2 of epirubicin (median: 850 mg/m2, range: 810-1320 mg/m2). The results of this study show that epirubicin is an active drug in advanced soft tissue sarcoma.

Adult↗

Phase II trial of idarubicin (4-demethoxydaunorubicin) in advanced breast cancer. The Clinical Screening Group of the European Organization for Research and Treatment of Cancer.

A phase II trial of idarubicin (IDR-4 demethoxydaunorubicin) was carried out in patients with advanced breast cancer. A dose of 45 mg/m2 was given orally once every 3 weeks. A total of 66 eligible patients were entered into the trial, 56 of whom were evaluable for response (65 were evaluable for toxicity at least). Therapeutic activity was demonstrated with an overall objective response rate of 21% (95% CI: 11-32%). When used as a first-line treatment, the response rate was 33% (95% CI: 9-57%) but this dropped to 17% when the treatment was administered after chemotherapy. Nausea-vomiting was the most frequent and severe non-hematological toxicity observed (WHO grade 3-4: 29%). Loss of hair was noticed in 48% of the patients but only 4% suffered from complete alopecia. Moderate myelotoxicity was reported but no cardiac dysfunction was noticed. IDR could be very advantageous as compared to other anthracyclines, due to its simplicity of administration associated with the lack of risk of extravasation or chemical phlebitis and also the possibility of it being able to reduce cardiotoxicity. Even if the equiefficacy of IDR and DXR has not, as yet, been clearly demonstrated, IDR should be chosen with preference to DXR when administration is not suitable.

Adult↗

Biochemical exploration of azoospermia: interest of the seminal transferrin assay.

Seminal transferrin is considered a good index of Sertoli cell function. In this study, including 19 control subjects, four vasectomized subjects and 65 non-vasectomized subjects with azoospermia, transferrin was measured concomitantly with other classical biochemical seminal markers such as L-carnitine, fructose and zinc. This parameter should provide additional information for differentiation between obstructive and non-obstructive azoospermia. A threshold value of 85 micrograms/ejaculate for transferrin was defined in the control and the vasectomized groups. The 65 subjects with azoospermia were divided into five groups according to L-carnitine and transferrin threshold values; the nature of azoospermia (obstructive or non-obstructive) was considered in each group. In the biological investigation of sterility, the measurement of transferrin provided information as to the aetiology of azoospermia. However, the determination of L-carnitine and fructose remains important in the localization of any obstruction.

Adult↗

[What are the prognostic factors in operable breast cancer without histologic axillary lymph node invasiveness. Results of an uni- and multifactorial analysis].

Between October 1977 and December 1983, 379 consecutive patients have been treated for unilateral, non metastatic breast cancer, either with conservative (n = 205) or radical surgery (n = 174), with axillary dissection in all the cases. None of them had histologically proved lymph node involvement. Adjuvant radiotherapy was given in 268 cases. Estrogen receptor (ER) and progesterone receptor (PR) levels were measured on each tumor. Levels greater than 5 fmoles/mg cytosolic protein were considered as positive for both ER and PR. At 5 years, overall survival (OS) and disease-free survival (DFS) are respectively 88% and 79%. Unifactorial analysis using KAPLAN and MEIER estimates and Logrank test revealed that OS was significantly related to age, tumor size, histopathological grading, ER and PR. DFS was significantly related to the same factors. Menopausal status, number of intra mammary tumor foci, previous familial history of breast cancer were not significant. Multifactorial analysis revealed that DFS was significantly related to age (bad prognosis [bp]: less than or equal to 37 years old), tumor size, histopathological grading (bp: SBR = 3) and that OS was significantly related to tumor size and PR (bp: PR less than or equal to 5 fmoles/mg protein). A prognostic score was obtained which sampled our patients into 3 significantly different (P less than 0.0001) groups with high, intermediate and low risk of relapse. These results suggest that tumor size, histopathological grading and PR have their own prognostic weight in histologically node negative breast cancer. Grouping these factors together allows to define a high risk relapse group that could benefit from adjuvant treatment.

Actuarial Analysis↗

[Human calcitonin in neoplastic hypercalcemia. Results of a prospective randomized trial].

Forty patients with hypercalcaemia (2.75 to 3.5 mmoles/l) due to bone metastases or to a neoplastic syndrome were treated with synthetic human calcitonin after previous hyperhydration. On entering the study, the patients were allocated at random to either an 0.5 mg dose or a 1 mg dose of the compound administered 6-hourly by the intravenous route. Calcemia was measured every 6 hours: if it became normal, treatment was discontinued 12 hours later, but if after 3 injections the blood calcium level had not been reduced by more than 0.4 mmoles/l, incremental doses of calcitonin were given. Synthetic human calcitonin reduced calcemia by more than 0.4 mmoles/l in 22 patients (group 1) and brought it down to normal value in 18 of these 8 hours on average after the first injection. A new rise in calcemia was observed in 12/18 cases 44 hours on average after treatment was discontinued. Reduction of calcemia by less than 0.4 mmoles/l was observed in 11 patients (group 2). Treatment was ineffective in 7 patients (group 3). There were no significant differences between the 3 groups in mean values and variances of the initial blood calcium levels. Whatever the initial dose of calcitonin, the therapeutic effect was obtained within the first 24 hours of treatment. In patients with incomplete results increasing the dosage did not result in a further reduction of calcemia. No hypocalcaemia was observed. This study confirms that synthetic human calcitonin has a normalizing effect on calcemia. This effect is not dose-dependent, and blood calcium levels rise again after treatment is discontinued.

Adult↗

Prognostic value of estrogen and progesterone receptors in operable breast cancer. Results of a univariate and multivariate analysis.

From October 1977 to December 1983, estrogen receptor (ER) and progesterone receptor (PR) levels were measured in 645 tumors from women with primary, unilateral, nonmetastatic breast cancer. All of them were treated surgically. Some received adjuvant radiotherapy, adjuvant chemotherapy, or adjuvant hormonotherapy. A level of greater than 5 fmol/mg cytosolic protein was considered as positive for both ER and PR. Unifactorial analysis, using Kaplan and Meier estimates and the log-rank test, revealed that disease-free survival (DFS) and overall survival (SV) were both strongly related to age, tumor size, nodal status, nodal effraction, histopathologic grading (SBR), ER, and PR. Menopausal status and number of intramammary tumor foci were not significant. Multifactorial analysis, using Cox's model, revealed a strong relationship between SV and age (poor prognosis [pp]: less than or equal to 37 years old), menopausal status (pp: postmenopausal) tumor size, nodal status (pp: N+ greater than 3), nodal effraction, ER (pp: less than or equal to 5 fmol/mg), histopathologic grading (pp: SBR = 3), and PR (pp: less than or equal to 5 fmol/mg). Similarly, multifactorial analysis revealed a strong correlation between DFS and age, tumor size, nodal status, nodal effraction, histopathologic grading, and PR. A prognostic score taking into account these prognostic factors was calculated for DFS and SV. Analysis of this score allowed us to divide our patients into four significantly different (P less than 0.0001) groups with high, intermediate, and low risk of relapse. Our procedure was then validated using the sample test technique. These results show that both ER and PR have their own prognostic weight and should be considered, among other classic prognostic factors, when adjuvant therapies are indicated after surgical treatment of breast cancer.

Adult↗

[Chemotherapy combining vindesine, thiotepa and methotrexate in metastatic breast cancer after failure of a combination containing anthracycline. Results of a prospective phase II trial].

Twenty-six patients with metastatic breast cancer where treated, after failure of a first line chemotherapy including an anthracycline, with a second line combination of vindesine, methotrexate and thiotepa. Overall tolerance of this treatment was good. There were one complete response and two partial responses. The authors conclude that this treatment has a marginal activity.

Adult↗

[Prognostic value of estrogen and progesterone receptors in the operable breast cancer: results of a uni- and multifactorial analysis].

This study concerns 645 patients first treated with surgery for unilateral, non metastatic, invading breast cancer. Intratumoral estrogen receptor and progesterone level were determined in every case. Level greater than 5 fmoles/mg cytosolic protein was considered as positive for both receptors. Univariate analysis has pointed out a significant linkage between overall survival and the following factors: age, clinical size of the tumor, histopathological grading SBR, clinical and histological lymph node involvement, capsular tear, RO and RP status. Statistical significance of menopausal status is borderline. Number of tumor foci is not significant. Likewise, disease free survival was correlated to the same factors. Multivariate analysis (Cox), secondarily pointed out that overall survival was strongly related to age, size of the tumor, lymph node involvement, capsular tear, histopathological grading SBR, menopausal status and RP. Multivariate analysis of the disease free survival revealed that it was strongly related to age, tumor size, lymph node involvement, capsular tear, grading SBR and RP. An interaction has been pointed out between Ro and menopausal status: Ro greater than 5 fmoles/mg cytosolic protein carry its own prognostic weight (Cox) and lengthen overall survival only for post menopausal women. A prognostic score, taking into account all of these factors has been calculated for both overall survival and disease free survival, and enabled us to isolate 4 groups of patients with good, intermediate and bad prognosis. These 2 models have been validated on an independent group of patients according to the sample test procedure. This results indicate that hormonal receptors carry their own prognostic weight in operable breast cancer (only for postmenopausal women for RO), and should be taken into account when adjuvant therapies are indicated after surgical treatment for breast cancer, in association with other more usual prognostic factors.

Adult↗

Inflammatory breast cancer. Determination of prognostic factors by univariate and multivariate analysis.

Between January 1977 and June 1983, 64 consecutive patients were treated for unilateral inflammatory nonmetastatic breast cancer. Our protocol included three or four courses of induction chemotherapy, then locoregional irradiation therapy with Co-60, followed by maintenance chemotherapy only if induction chemotherapy had proven effective. Eight patients with a residual tumor after radiotherapy underwent a modified radical mastectomy. Actuarial 3-year overall survival for the whole group was 38%, and the median disease-free survival time was 19 months. The effect of 17 factors on overall survival or disease-free survival was analyzed. With univariate analysis, eight factors were found to affect overall survival or disease-free survival: extent of initial erythema, size of initial edema, lymph node involvement, erythema present at the end of initial chemotherapy, erythema present at the end of radiotherapy, tumor size at the end of induction chemotherapy, residual breast tumor at the end of maintenance chemotherapy, and performance of a radical mastectomy. Age at diagnosis, menopausal status, type of chemotherapy, and date of appearance of inflammatory signs did not influence prognosis. Multivariate analysis using the Cox proportional hazard model isolated three bad prognosis factors: erythema involving the whole breast at initial diagnosis, erythema present at the end of initial chemotherapy, and lymph node involvement.

Actuarial Analysis↗

[Inflammatory cancer of the breast].

The so-called inflammatory carcinoma of the breast is a rare condition characterized, in almost every case, by metastatic diffusion in numerous organs. Clinical criteria are indispensable to establish a diagnosis which is not ruled out by a negative skin biopsy. Radiotherapy or surgery, or both, gives disappointing results with a median survival of about 18 months and a 5-year survival rate of 5%. It is unanimously agreed that adding chemotherapy to these methods improves local control and increases the 5-year survival rate. The optimal treatment remains to be determined by co-operative studies.

Biopsy↗

[Adjuvant chemotherapy of breast cancer].

Adjuvant chemotherapy completes the local treatment of breast cancer and aims at reducing recurrences and improving the survival rate of high risk patients. As its present benefits mainly apply to the free interval and to some categories of subjects, further controlled study is required to assess its value.

Antineoplastic Combined Chemotherapy Protocols↗

Phase II clinical evaluation of doxifluridine.

Disease-oriented phase II trials of doxifluridine were performed in advanced colorectal, breast, renal, endometrial, stomach, and ovarian carcinomas. The dose schedule recommended by the phase I trial (12.5 g/m2 by continuous iv infusion over 6 hours once a week for 3 weeks followed by a 1-week rest) was chosen first: the initial dose was later decreased to 10 g/m2 due to the fact that several neurotoxic effects were reported. A total of 207 patients were entered: 137 patients who received at least two courses of treatment were evaluable for response. Therapeutic activity was demonstrated in breast cancer [two complete responses (CR) and 13 partial responses (PR) among 42 patients], colon cancer (seven PRs among 35 patients), and rectal cancer (six PRs among 23 patients). Some therapeutic activity was detected in ovarian cancer (one CR among nine patients), endometrial cancer (one PR among five patients), and stomach cancer (one PR among five patients). No significant activity was noticed in renal cancer (one PR among 18 patients). Nonhematological toxicity was evaluated according to World Health Organization criteria. Nausea and vomiting were recorded in 50% of the patients (Grade 3-4 in 5%), diarrhea was recorded in 20% (Grade 3-4 in 5%), and cutaneous and allergic reactions were recorded in 10% (Grade 3-4 in 2%). Myelotoxicity during the first treatment course was mild; median wbc and platelet count nadirs (x 10(9) cells/L) were 4.1 (range, 0.1-11) and 194 (range, 20-482), respectively. Nevertheless, some cases of acute leukopenia and thrombopenia were reported. Consciousness alterations and neurologic symptoms were the major side effects (72 of 173 evaluable patients), since treatment had to be interrupted in 34 patients and four lethal neurotoxic effects occurred. At the same total dose of doxifluridine, the risk of neurotoxicity significantly increases with age and with the weekly dose and to the contrary it decreases with increasing bilirubin level. Although activity was demonstrated, this treatment cannot be recommended because of major neurotoxicity. Further pharmacological studies seem warranted to define the optimal dosage schedule and to obtain a better therapeutic index.

Adult↗

[Rapidly growing breast cancer: results of a retrospective analysis with a study of prognostic factors].

Between January 1977 and December 1982, 66 consecutive patients have been treated for unilateral, rapidly progressing, non metastatic breast cancer. They were divided into three groups: Group A (n = 10): tumor whom volume had increased during the 2 months before diagnosis; Group B (n = 30): inflammatory signs (erythema, skin oedema, elevated local temperature) involving less than one half of the breast; Group C (n = 26): inflammatory signs involving more than one half of the breast. All patients where managed similarly: 3 to 4 courses of chemotherapy (CMF: n = 24; AVCF: n = 42), then loco regional irradiation therapy with cobalt 60, followed by maintenance chemotherapy, only if the first chemotherapy had proved effective (CMF: n = 13; AVCF: n = 27). Nine patients with residual tumor after radiotherapy underwent mastectomy with axillary dissection. The actuarial 5 years survival for the whole group is 29%, and respectively 49%, 38% and 9% for the groups A, B and C. The median disease free intervals are 43, 29 and 12 months respectively. Fifteen prognostic factors likely to influence overall survival or disease free survival were evaluated. With univariate analysis, 8 factors were found to be of individual prognostic value: extent of initial erythema, erythema present after initial chemotherapy, erythema present after radiotherapy, non menopaused status, tumor diameter greater than 10 cms, residual breast tumor (clinical or radiographic) after maintenance chemotherapy, supra clavicular adenopathy (N3). Age at the diagnosis, type of chemotherapy, or performance of a radical mastectomy did not influence the prognosis. Multivariate analysis using the Cox-model isolated 3 factors of bad prognosis: erythema involving the whole breast at initial diagnosis, erythema present at the end of initial chemotherapy, N3.

Adult↗

An EORTC phase II study of mitoxantrone in solid tumors and lymphomas.

Mitoxantrone is an anthracenedione, showing structural similarities to doxorubicin. This drug has been proved active against several tumor systems, including some tumors resistant to doxorubicin, and also against human breast xenografts. It is also less cardiotoxic than doxorubicin. Mitoxantrone has been given to 335 patients in an i.v. perfusion of 12 mg/m2 or 14 mg/m2 every 3 weeks. Two hundred and sixty-three patients with advanced disease were evaluable for response: breast (94 patients), head and neck (40), kidney (20), bronchial (19), lymphomas (13) and various sites (77). Most of the patients had been previously treated with radiotherapy and chemotherapy, including/not including doxorubicin. In breast cancer three complete remissions (CR) and 16 partial remissions (PR) have been achieved (20%). The therapeutic activity was higher in patients who had not received any prior chemotherapy: 35 vs 15% (P = 0.06). The response rate observed at 14 mg/m2 (32%) was superior to the response rate observed at 12 mg/m2 (15%). However, no response has been reported in lung metastases (0/22). The median duration of response is 8 months. Mitoxantrone shows borderline activity in head and neck tumors (one CR and two PR out of 40 patients) but no activity in squamous cells of the lung (0/19). One CR and three PR have been seen out of 13 malignant lymphomas (four Hodgkin's disease and nine non-Hodgkin's lymphomas). The duration of response ranges from 10 to 24+ months. Myelosuppression was moderate and no severe leukopenia has been reported. Nausea and vomiting were seen in 50% of the patients. Four patients presented cardiac events associated with mitoxantrone, such as reversible congestive heart failure or a significant decrease in the ventricular ejection fraction. Alopecia was observed in 17 and 48% of the patients treated with 12 and 14 mg/m2 respectively. Due to its anti-tumoral activity, mainly in breast cancer, and its low hematological and cardiac toxicity, mitoxantrone must be considered as a major antimitotic.

Adolescent↗