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ABSTRACT: To determine the risk factors for EDin men treated by prostate brachytherapy (PB) for localized prostate cancer and to propose a model to predict post-implant erectile function. Out of a series of 270 sexually active men treated by PB, 241 (89%) (mean age=66 years (range, 43-80)) accepted to participate in a mail-based study on erectile function. The risk factors for erectile dysfunction were determined by regression analysis and a predictive model was proposed. The performance of the model was determined in this population and subsequently verified in a population of 50 men treated by PB in another treatment center. The risk factors for ED after PB were age, the pre-implant IIEF score and prostate volume. In the studied population, the final model to predict a post-treatment IIEF-5 score, using these factors, had a sensitivity of 69% and a specificity of 68% associated to an area under the ROC curve (AUC) of 0.75. The same performance was obtained in another treatment center. Age, pre-implant IIEF-5 score and prostate volume may be used to predict post-implant erectile function in patients treated by PB.International Journal of Impotence Research advance online publication, 28 February 2013; doi:10.1038/ijir.2013.3.
International journal of impotence research 02/2013; · 2.73 Impact Factor
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P Pommier,
M Morelle,
L Perrier,
R de Crevoisier,
A Laplanche,
P Dudouet,
M-A Mahé,
B Chauvet,
T-D Nguyen,
G Créhange,
A Zawadi,
O Chapet,
I Latorzeff,
A Bossi,
V Beckendorf,
E Touboul,
X Muracciole, J-M Bachaud,
S Supiot,
J-L Lagrange
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ABSTRACT: The main objective of the economical study was to prospectively and randomly assess the additional costs of daily versus weekly patient positioning quality control in image-guided radiotherapy (IGRT), taking into account the modalities of the 3D-imaging: tomography (CBCT) or gold seeds implants. A secondary objective was to prospectively assess the additional costs of 3D versus 2D imaging with portal imaging for patient positioning controls.
Economics data are issued from a multicenter randomized medico-economics trial comparing the two frequencies of patient positioning control during prostate IGRT. A prospective cohort with patient positioning control with PI (control group) was constituted for the cost comparison between 3D (IGRT) versus 2D imaging. The economical evaluation was focused to the radiotherapy direct costs, adopting the hospital's point of view and using a microcosting method applied to the parameters that may lead to cost differences between evaluated strategies.
The economical analysis included a total of 241 patients enrolled between 2007 and 2011 in seven centres, 183 in the randomized study (128 with CBCT and 55 with fiducial markers) and 58 in the control group. Compared to weekly controls, the average additional cost per patient of daily controls was €847 (CBCT) and €179 (markers). Compared to PI, the average additional cost per patient was €1392 (CBCT) and €997 (fiducial markers) for daily controls; €545 (CBCT) and €818 (markers) in case of weekly controls.
A daily frequency for image control in IGRT and 3D images patient positioning control (IGRT) for prostate cancer lead to significant additional cost compared to weekly control and 2D imaging (PI). Long-term clinical assessment will permit to assess the medico-economical ratio of these innovative radiotherapy modalities.
Cancer/Radiothérapie 08/2012; 16(5-6):444-51. · 1.49 Impact Factor
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ABSTRACT: Preservation of fertility in men of middle age is an issue that is experiencing a growing interest. Prostate cancer is the second most common cancer in men and is diagnosed earlier than before. Brachytherapy is a treatment for prostate cancer that preserves ejaculation. Our aim was to study the fertility of men treated with prostate brachytherapy in order to improve patient information.
In a series of 270 sexually active men with localized prostate cancer treated with brachytherapy (permanent implants of Iode 125) at the Institute Claudius Regaud between 2000 and 2006, mean age 65 years (43-80), four patients spontaneously expressed their interest in the preservation of fertility and had an andrological evaluation.
Four patients were aged 43, 48, 57 and 61 years, all working (including two businessmen), their partner was aged respectively 42, 37, 47 and 38 years. All four had a post-treatment semen analysis (done over a year after brachytherapy) rich in spermatozoa, with moderate asthenospermia, the main anomaly being severe hypospermia. These spermiograms were nonetheless consistent with the occurrence of spontaneous pregnancy (occurrence of miscarriage in the patient 1).
There is an interest in applying to men with prostate cancer their position on fertility in order to inform them about the morbidity of various treatments, options for fertility preservation, and the need to continue a contraception after brachytherapy if the partner is not menopausal.
Progrès en Urologie 01/2012; 22(1):53-7. · 0.58 Impact Factor
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B Delaunay,
M Delannes,
A Salloum,
D Delavierre,
F Wagner,
F Jonca,
M Thoulouzan,
P Plante, J-M Bachaud,
M Soulie,
E Huyghe
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ABSTRACT: Orgasm is a domain of male sexuality that remains underreported in literature. Our aim was to realize the first detailed analysis of orgasm in patients treated by 125 I permanent prostate brachytherapy for localized prostate cancer.
In a series of 270 sexually active men treated by prostate brachytherapy (125I permanent implantation), 241 (89%), mean age of 65 (43-80), participated in a mailed survey about sexual function after a mean time of 36 months (9-70). Erectile and ejaculatory functions and orgasm were explored using a mailed questionnaire. Two questions focused on orgasm. The first was about quality of orgasm (fast/intense/late, difficult/weak/absent) and the second about the presence of painful orgasm and its frequency (always/sometimes/often).
After prostate brachytherapy, 81.3% of sexually active men conserved ejaculation and 90% orgasm. There was a significant deterioration of the quality of orgasm (P=0.0001). More than 50% of the patients had an altered orgasm (weak, difficult, absent) after brachytherapy, vs 16% before implantation (P=0.001). Men with a diminished ejaculation volume often had a weak/difficult orgasm (P=0.007). Neoadjuvant hormonal therapy did not seem to impact the quality of orgasm or the frequency of painful ejaculation. Patients who had an IIEF-5 score higher than 12 had frequently intense orgasm (26.7% vs 2.7%; P<0.001) after brachytherapy. Sixty patients (30.3%) experienced often/sometimes painful ejaculation 12.9% (n=31) before implantation (P=0.0001).
Most of the patients treated by prostate brachytherapy conserved orgasm after treatment. However, most of the patients described a deterioration of the quality of orgasm.
Progrès en Urologie 12/2011; 21(13):932-9. · 0.58 Impact Factor
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ABSTRACT: Knowing the importance of sexuality items in the choice by the patient of the modality of treatment of localized prostate cancer, we aimed at reviewing and updating the effects of prostate radiotherapy and brachytherapy on sexual functions.
A PubMed search was done using the keywords: prostate cancer, erectile dysfunction, radiotherapy, brachytherapy, ejaculation and orgasm.
After both radiotherapy and brachytherapy, sexual troubles occur progressively, the onset of occurrence of erectile dysfunction being 12-18 months after both treatments. Even though the pathophysiological pathways by which radiotherapy and brachytherapy result in erectile dysfunction have not yet been fully clarified, arterial damage and exposure of neurovascular bundle to high levels of radiation seem to be two main causes of erectile dysfunction after radiotherapy and brachytherapy. The radiation dose received by the corpora cavernosa at the crurae of the penis may also be important in the etiology of erectile dysfunction. Another important factor following radiotherapy is the treatment modality. Not many data about ejaculation and orgasm after radiation treatments have been published yet. Recent data show that most of the population treated by brachytherapy conserves ejaculation and orgasm after treatment, even if a majority describe reduction of volume and deterioration of orgasm. Patients need to be correctly informed on the possible sequela of radiotherapy and brachytherapy on their sexual well-being while planning their treatment. Patients should also be informed about the possible treatment modalities for erectile dysfunction.
Progrès en Urologie 12/2009; 19 Suppl 4:S173-6. · 0.58 Impact Factor
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ABSTRACT: Purpose: No biological signature of chemo-radiotherapy sensitivity has been reported for patients with locally advanced non-small cell lung cancer (NSCLC). We have previously demonstrated that basic fibroblast growth factor (FGF-2) and alphavbeta3 integrin pathways control tumor radioresistance. We now investigate whether the expression of the proteins involved in these pathways may be associated with the response to treatment and, therefore, the clinical outcome. Methods: FGF-2, alpha3 integrin, angiopoietin-2 and syndecan-1 expressions were studied using immunohistochemistry performed on biopsies obtained, before any treatment, from 65 patients exclusively treated with chemo-radiotherapy for locally advanced NSCLC. Response to treatments was evaluated according to the RECIST criteria by CT-scan at least 6 weeks after the end of the chemo-radiotherapy. Local progression, metastasis and disease-free survivals were studied using log rank test and Cox proportional hazard analysis. Results: Among this NSCLC biopsy population, 43.7% over- expressed alpha3 integrin (alpha 3+), 43% FGF-2 (FGF-2+), 41.5% syndecan-1 and 59.4% angiopoietin-2. Our results show a strong association between FGF-2 and alpha 3 integrin expression (P=0,001). The adjusted hazard ratio of local recurrence of alpha3 +/ FGF-2+ tumors compared to FGF-2-/ alpha 3- tumors was 6.1 (95% confidential interval=2.6 to 14.6, P=0,005) whereas the risk of local recurrence was not increased when tumors overexpressed alpha 3 or FGF-2 alone. Moreover, the co-expression of these two proteins is marginally associated with the response to chemo-radiotherapy and to metastasis free survival. Conclusion: This study identifies the combined profile FGF-2/alpha 3 integrin expression as a signature of the local control in patients treated with chemo-radiotherapy for locally-advanced NSCLC.
Revue des Maladies Respiratoires 12/2008; 25(9):1176. · 0.59 Impact Factor
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ABSTRACT: To determine the survival and prognosis criteria of pT3NxM0 prostate tumours (TNM 2002) after radical retropubic prostatectomy (RRP).
Between 1988 and 2000, 606 consecutive RRP were performed for T1-3 tumours, whose 246 (40.6%) specimens were classified pT3, followed in 53 cases by adjuvant radiotherapy and in 71 cases by salvage radiotherapy. Fifty-five patients received postoperative hormonotherapy at the time of biochemical recurrence. Biochemical recurrence was determined by two PSA values greater than 0.2 ng/ml.
Mean age of this group was 65 years at surgery. Mean follow-up was 91.4 months. Mean preoperative PSA was 12.8 ng/ml. Distribution of cases was 170 pT3a (69.1%) and 76 (30,9%). At 10 years, the biochemical progression-free, metastasis-free, specific and overall survival was 54, 86, 92 and 75% respectively. Worse biochemical prognostic factors were lymph node extension, high Gleason score, high preoperative PSA, seminal vesicles involvement, positive surgical margins and adjuvant radiotherapy absence.
This study shows that pT3 tumours treated with therapeutic associations including RRP presents an excellent specific survival at 10 years. The determination of biochemical recurrence prognostic factors could help to select patients who need complementary treatments after surgery.
Progrès en Urologie 11/2008; 18(9):586-94. · 0.58 Impact Factor
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P Pommier,
M Delannes,
O LeFloch,
V Bernier,
M-H Baron,
L Thomas,
C Malet,
J Bonnet,
P Louisot,
P Aletti, [......],
F Chirat,
S Lebivic,
X Montbarbon, J-M Bachaud,
L Votron,
O Lasbareilles,
O Desmettre,
G Bringeon,
F Gassa,
D Peiffert
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ABSTRACT: To analyse a new technique for prostate brachytherapy with permanent Iodine implants characterized by the use of a seed projector after a 3D dosimetric peroperative treatment planning (FIRST technique).
395 patients have been treated in France with this technique in six radiotherapy centres between November 2002 and December 2005 for a localized prostate cancer.
Thirteen patients (3.3%) developped a urinary retention, and respectively 7.8 and 26.5% an acute RTOG grade 3 and 2 toxicity. The 6-weeks IPSS score was equal or lower to 15 in 73% with a 11 median IPSS value. A failure of the loading with the seed-projector, leading to a manual loading of the seeds, occurred in 9 patients (2.3%) in two centres, directly related to the loading procedure with the seed-projector in 5 cases. The median duration of the procedure was reduced by 30 minutes for the patients treated in 2005.
This multicenter study establishes the feasibility of the routine use of a seed projector for permanent iodine 125 prostate implants with an initial tolerance similar to the best results published for other implants techniques.
Cancer/Radiothérapie 01/2007; 10(8):559-64. · 1.49 Impact Factor
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Clinical Nuclear Medicine 06/2006; 31(5):284-8. · 3.67 Impact Factor
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ABSTRACT: Traditional radiation treatment planning relies on density imaging such as Computed Tomography for anatomic information of various structures of interest including target and normal tissues. However, the difficulties to distinguish malignant from normal tissue on CT slides often leads to inaccurate outlining of the GTV and/or to geographic misses. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has shown an increase in both sensitivity and specificity over CT in locoregional staging of patients with non-small cell lung cancer (NSCLC). The co registration of FDG-PET images to the data of the CT planning offers the radiation oncologist the possibility to include functional information into the target outlining. For the treatment of patients with NSCLC, it has been shown that the use of FDG-PET images: 1) modified the shape and volume of radiation fields in 22-62% of cases, mainly due to a better nodal staging and distinction of atelectasis from tumor and; 2) significatively reduced the interobserver and intraobserver variability. This paper reviews the results reported in the literature. Challenges and proposed solutions are discussed.
Cancer/Radiothérapie 01/2006; 9(8):602-9. · 1.49 Impact Factor
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A Villers,
P Pommier,
A Bataillard,
B Fervers, J M Bachaud,
N Berger,
A F Bertrand,
R Bouvier,
D Brune,
A Daver, [......],
J L Lagrange,
V Molinie,
J P Muratet,
P Pabot du Chatelard,
M Peneau,
D Prapotnich,
V Ravery,
P Richaud,
D Rossi,
M Soulie
British Journal of Cancer 09/2003; 89 Suppl 1:S50-8. · 5.04 Impact Factor
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ABSTRACT: The aim of our study was to describe the main characteristics of bronchioloalveolar carcinoma (BAC) in the light of the latest WHO classification. The clinical, pathological and radiological features of 16 consecutive resected cases of early BAC (stage IA) were reviewed.
Retrospective pathology of 249 adenocarcinomas over a 32 months period.
Computerised tomography (CT) features which supported a diagnosis of BAC included a peripheral location, irregular margins forming a star pattern, pleural tagging, ground-glass attenuation and an air bronchogram. Immunochemistry was positive in all cases for cytokeratins 7 and 19, EMA and TTF-1, but was only variably positive for ACE, P53 and MIB-1. For 14 out of 16 patients clinical outcome was favourable with no evidence to date of recurrence since surgery. Of the others, one developed extra-thoracic metastases and the other a local recurrence requiring further surgery.
Recognising these characteristics of BAC is important as early diagnosis and treatment of this condition can be associated with an excellent prognosis.
Revue des Maladies Respiratoires 03/2003; 20(1 Pt 1):61-7. · 0.59 Impact Factor
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V Beckendorf, J M Bachaud,
P Bey,
S Bourdin,
C Carrie,
O Chapet,
D Cowen,
S Guérif,
H M Hay,
J L Lagrange,
P Maingon,
E Le Prisé,
P Pommier,
J M Simon
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ABSTRACT: The delineation of target volume and organs at risk depends on the organs definition, and on the modalities for the CT-scan acquisition. Inter-observer variability in the delineation may be large, especially when patient's anatomy is unusual. During the two french multicentric studies of conformal radiotherapy for localized prostate cancer, it was made an effort to harmonize the delineation of the target volumes and organs at risk. Two cases were proposed for delineation during two workshops. In the first case, the mean prostate volume was 46.5 mL (extreme: 31.7-61.3), the mean prostate and seminal vesicles volume was 74.7 mL (extreme: 59.6-80.3), the rectal and bladder walls varied respectively in proportion from 1 to 1.45 and from 1 to 1.16; in the second case, the mean prostate volume was 53.1 mL (extreme: 40.8-73.1), the volume of prostate plus seminal vesicles was 65.1 mL (extreme: 53.2-89), the rectal wall varied proportionally from 1 to 1, 24 and the vesical wall varied from 1 to 1.67. For participating centers to the french studies of dose escalation, a quality control of contours was performed to decrease the inter-observer variability. The ways to reduce the discrepancies of volumes delineation, between different observers, are discussed. A better quality of the CT images, use of urethral opacification, and consensual definition of clinical target volumes and organs at risk may contribute to that improvement.
Cancer/Radiothérapie 12/2002; 6 Suppl 1:78s-92s. · 1.49 Impact Factor
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P Pommier,
A Villers,
A Bataillard,
D Brune,
B Fervers, J M Bachaud,
N Berger,
A F Bertrand,
R Bouvier,
A Daver, [......],
J L Lagrange,
V Molinié,
J P Muratet,
P Pabot du Chatelard,
M Peneau,
D Prapotnitch,
V Ravery,
P Richaud,
D Rossi,
M Soulié
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ABSTRACT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical speciality societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery.
Produce clinical practice guidelines for the radiotherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project.
The FNCLCC and the French Urology Association (AFU) designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers.
The main recommendations are: 1/ a minimal dose of 70 Gy must be used, whatever the prognostic factors; 2/ it appeared that patients with favourable prognostic indicators (stage T1-2, PSA < or = 10 micrograms/L and Gleason score < or = 6) do not benefit from a dose escalation effect for doses over 70-74 Gy; 3/ patients with intermediate prognosis are the ones who benefit most from the dose escalation effect over 74 Gy, provided they receive exclusive radiation therapy; 4/ whenever possible, patients should be included in controlled trials designed to assess the effects of dose escalation and hormonotherapy.
Cancer/Radiothérapie 05/2002; 6(2):119-26. · 1.49 Impact Factor
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P Pommier,
A Villers,
A Bataillard,
D Brune,
B Fervers, J M Bachaud,
N Berger,
A F Bertrand,
R Bouvier,
A Daver, [......],
J L Lagrange,
V Molinié,
J P Muratet,
P Pabot du Chatelard,
M Peneau,
D Prapotnitch,
V Ravery,
P Richaud,
D Rossi,
J Y Soret
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[hide abstract]
ABSTRACT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical specialty societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by a critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery.
Produce clinical practice guidelines for the brachytherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project.
The FNCLCC and the French Urology Association (AFU) first designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers.
The main recommendations are: 1/Brachytherapy with permanent seeds alone is a possible curative treatment for prostate cancer patients with the following prognosis factors: tumour stage T1 or T2a (TNM 1992), Gleason score < or = 6 and PSA < 10 micrograms/L. 2/Combined treatment with brachytherapy and hormonal therapy could be more efficient than brachytherapy alone for prostate cancer patients with Gleason score > 7 and/or PSA > 10.3/Combination of brachytherapy and external beam radiation therapy can be proposed to prostate cancer patients with intermediate prognosis. 4/Before and after seed implantation, risks of infection must be prevented by appropriate antibiotic therapy (recommendation). 5/Brachytherapy must not be performed within 2 months of transurethral prostate resection. 6/The height of the urethra receiving more than 200% of the prescribed dose must be reported. The portion of the rectum receiving 100 and 120% of the prescribed dose must be limited to 10 and 5 mm length, respectively.
Cancer/Radiothérapie 12/2001; 5(6):770-86. · 1.49 Impact Factor
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ABSTRACT: Electrochemotherapy is a new anticancer therapy in which transient permeabilization of cells by an electric field induces a significant increase in the bleomycin concentration and toxicity in tumour cells. We report a clinical study of electrochemotherapy in malignant melanoma. The main issues addressed were the effect of the size of the nodules, the optimization of the electrical parameters, and posttreatment clinical observations. Four patients were enrolled in the study. They received a 10 mg/m2 dose of bleomycin administered intravenously, followed by short, intense electric pulses applied directly to the skin at the tumour sites. Antitumour effects were obtained, especially in the smallest nodules. Objective responses were obtained in more than 90% of the 55 nodules treated, with a complete response rate of 9%. All patients tolerated the treatment well. No residual effects from the electric pulses were observed, even when a high number of pulses were required or when two consecutive treatments were applied. These results are encouraging and the study should be continued.
Melanoma Research 11/2000; 10(5):468-74. · 2.19 Impact Factor
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ABSTRACT: To determine the incidence of second non-germ-cell cancers (SNGC) in patients treated for stage I-II testicular seminoma.
This study is based on 131 evaluable patients treated at the Institut Claudius Regaud between 1970 and 1990. Treatment modalities, including salvage therapy for 6 patients developing recurrence, were as follows: infradiaphragmatic irradiation (infraDI) only in 55 cases, infra- and supradiaphragmatic irradiation (infraDI + supraDI) in 64 cases, and irradiation and chemotherapy (IC) in 12 cases. Five patients were lost to follow-up 4 months to 14 years after primary treatment (mean follow-up: 11 years). The cumulative incidence of SNGC was compared to the overall cancer incidence in the age-matched male population reported in the Tarn Cancer Registry. The relative risk was expressed as the Standardized Incidence Ratio (SIR).
The cumulative incidence of SNGC was 10.7% (14/131 patients). SIR was equal to 2.81 (p < 0.001) and increased with the duration of follow-up. SIR was significantly increased in 64 patients treated with infraDI + supraDI (SIR) = 3.25; p = 0.002), but not in the 55 patients treated with infraDI only (SIR = 0.62; p = 0.8). The 12 treated patients with IC had an SIR of 26.2 (p < 0.001). Three of the 4 patients who developed a haematological malignancy belonged to the IC group.
The risk of SNGC is increased after infraDI + supraDI. The risk of SNGC after infraDI only is not increased with a median follow-up of 6 years, but this follow-up is too short to allow any definitive conclusions. The risk of SNGC and particularly haematological malignancy appears to be increased by the combination of radiotherapy and chemotherapy.
Progrès en Urologie 09/1999; 9(4):689-95. · 0.58 Impact Factor
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ABSTRACT: To measure the incidence of second non-germ cell malignancies (SNGCM) in patients treated for a stage I-II testicular seminoma.
From 1970 to 1992, 131 evaluable patients received in the Institut Claudius Regaud a post-orchiectomy treatment for a stage I-II testicular seminoma. The therapeutic modalities, including salvage treatment for six recurrences, were as follows: infradiaphragmatic radiotherapy (IDRT) (n = 55); infra- and supradiaphragmatic radiotherapy (IDRT + SDRT) (n = 64); IDRT + SDRT with chemotherapy (n = 12). The mean follow-up was 11 years. The cumulative incidence of SNGCM was compared to the overall cancer incidence in the general male population on the basis of the Tarn Cancer Registry; the relative risk was expressed as a standardized incidence ratio (SIR).
Overall, the cumulative incidence of SNGCM was 10.7% (14/131 cases). The SIR was equal to 2.81 (95% confidence interval (CI) 1.54-4.72; P < 0.001) and increased with follow-up duration. The SIR was significantly increased in 64 patients treated with IDRT + SDRT (SIR = 3.08; 95% CI 1.47-5.66; P = 0.002) but not in 55 patients treated with IDRT alone (SIR = 0.62; 95% CI 0.01-3.43; P = 0.8). The 12 patients who received chemotherapy had an SIR of 26.2 (95% CI 5.48-77.69; P < 0.001), while the SIR was 2.26 in the 119 patients who did not receive any chemotherapy (95% CI 1.13-4.04; P = 0.01 ). Of four hematologic malignancies, three appeared in the 12 patients who received chemotherapy.
An increased risk of SNGCM after SDRT + IDRT has been demonstrated. After IDRT alone, the risk of second cancer is not incremented after a median follow-up of 6 years, but further observation of the patients is necessary to achieve final conclusions. Our results suggest that the risk of second cancer and especially of hematologic malignancy is increased by the association of chemotherapy and radiation.
Radiotherapy and Oncology 02/1999; 50(2):191-7. · 5.58 Impact Factor
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L M Mir,
L F Glass,
G Sersa,
J Teissié,
C Domenge,
D Miklavcic,
M J Jaroszeski,
S Orlowski,
D S Reintgen,
Z Rudolf,
M Belehradek,
R Gilbert,
M P Rols,
J Belehradek, J M Bachaud,
R DeConti,
B Stabuc,
M Cemazar,
P Coninx,
R Heller
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ABSTRACT: Electrochemotherapy (ECT) enhances the effectiveness of chemotherapeutic agents by administering the drug in combination with short intense electric pulses. ECT is effective because electric pulses permeabilize tumour cell membranes and allow non-permeant drugs, such as bleomycin, to enter the cells. The aim of this study was to demonstrate the anti-tumour effectiveness of ECT with bleomycin on cutaneous and subcutaneous tumours. This article summarizes results obtained in independent clinical trials performed by five cancer centres. A total of 291 cutaneous or subcutaneous tumours of basal cell carcinoma (32), malignant melanoma (142), adenocarcinoma (30) and head and neck squamous cell carcinoma (87) were treated in 50 patients. Short and intense electric pulses were applied to tumours percutaneously after intravenous or intratumour administration of bleomycin. The tumours were measured and the response to the treatment evaluated 30 days after the treatment. Objective responses were obtained in 233 (85.3%) of the 273 evaluable tumours that were treated with ECT. Clinical complete responses were achieved in 154 (56.4%) tumours, and partial responses were observed in 79 (28.9%) tumours. The application of electric pulses to the patients was safe and well tolerated. An instantaneous contraction of the underlying muscles was noticed. Minimal adverse side-effects were observed. ECT was shown to be an effective local treatment. ECT was effective regardless of the histological type of the tumour. Therefore, ECT offers an approach to the treatment of cutaneous and subcutaneous tumours in patients with minimal adverse side-effects and with a high response rate.
British Journal of Cancer 07/1998; 77(12):2336-42. · 5.04 Impact Factor
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ABSTRACT: A population pharmacokinetics study using the NONMEM program was undertaken to determine the effects of different covariates on the pharmacokinetic parameters of etoposide. A total of 1,044 plasma etoposide concentrations were determined by high-performance liquid chromatography (HPLC) in 100 patients (pts; 75 men and 25 women aged 25-85 years) treated for various tumor types with i.v. (57 pts) or oral (43 pts) etoposide. For 67 pts, etoposide plasma protein binding was determined by equilibrium dialysis; the unbound fraction ranged from 4% to 24%. A linear two-compartment model with first-order absorption (for oral dosing) accurately described the concentration versus time data. The central and peripheral volumes of distribution were significantly correlated with the body surface area [Vc (L) = 5.5 x BSA (m2) and Vp = 4.1 x BSA], but even after BSA had been taken into account, the interindividual variability of the two volumes remained high (34% and 57%, respectively). The clearance (CL) was not correlated with the following covariates: age, BSA, sex, height, and levels of serum bilirubin and liver enzymes. The final regression model for CL was CL (ml/min) = 49.8 x (1 - 0.009 x PRO) x WT/Scr + 33.8 x (1 - 0.29 x META) x (1 - 0.012 x ALB), where ALB, PRO, WT, and Scr, respectively, were albuminemia, proteinemia (g/l), weight (kg), and serum creatinine (microM) and META = 1 if the patient had liver metastases (otherwise, META = 0). The interindividual variability in CL (mean value 30 ml/min) decreased only from 32% to 26% when these covariates were taken into account. The mean oral bioavailability was 66%, showing an interindividual variability of 37%. The plasma clearance of the unbound fraction was strongly and negatively correlated with Scr but was not dependent on either PRO or ALB. These data show that modifications in PRO levels do not directly affect plasma exposure to unbound etoposide. This analysis makes possible the rational consideration of modifications of covariates such as Scr in etoposide dosing. This population data base will constitute the prerequisite for adaptative control with feedback dosing for continuous oral administration of etoposide.
Cancer Chemotherapy and Pharmacology 02/1998; 41(2):125-32. · 2.83 Impact Factor
