-
Gwenaelle Gravis,
Karim Fizazi,
Florence Joly,
Stéphane Oudard,
Franck Priou,
Benjamin Esterni,
Igor Latorzeff,
Remy Delva,
Ivan Krakowski,
Brigitte Laguerre, [......],
Claude Linassier,
Jean Luc Labourey,
Jean Pascal Machiels,
Claude El Kouri,
Alain Ravaud,
Etienne Suc,
Jean Christophe Eymard,
Ali Hasbini,
Guilhem Bousquet,
Michel Soulie
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Early chemotherapy might improve the overall outcomes of patients with metastatic non-castrate (ie, hormone-sensitive) prostate cancer. We investigated the effects of the addition of docetaxel to androgen-deprivation therapy (ADT) for patients with metastatic non-castrate prostate cancer. METHODS: In this randomised, open-label, phase 3 study, we enrolled patients in 29 centres in France and one in Belgium. Eligible patients were older than 18 years and had histologically confirmed adenocarcinoma of the prostate and radiologically proven metastatic disease; a Karnofsky score of at least 70%; a life expectancy of at least 3 months; and adequate hepatic, haematological, and renal function. They were randomly assigned to receive to ADT (orchiectomy or luteinising hormone-releasing hormone agonists, alone or combined with non-steroidal antiandrogens) alone or in combination with docetaxel (75 mg/m(2) intravenously on the first day of each 21-day cycle; up to nine cycles). Patients were randomised in a 1:1 ratio, with dynamic minimisation to minimise imbalances in previous systemic treatment with ADT, chemotherapy for local disease or isolated rising concentration of serum prostate-specific antigen, and Glass risk groups. Patients, physicians, and data analysts were not masked to treatment allocation. The primary endpoint was overall survival. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00104715. FINDINGS: Between Oct 18, 2004, and Dec 31, 2008, 192 patients were randomly allocated to receive ADT plus docetaxel and 193 to receive ADT alone. Median follow-up was 50 months (IQR 39-63). Median overall survival was 58·9 months (95% CI 50·8-69·1) in the group given ADT plus docetaxel and 54·2 months (42·2-not reached) in that given ADT alone (hazard ratio 1·01, 95% CI 0·75-1·36). 72 serious adverse events were reported in the group given ADT plus docetaxel, of which the most frequent were neutropenia (40 [21%]), febrile neutropenia (six [3%]), abnormal liver function tests (three [2%]), and neutropenia with infection (two [1%]). Four treatment-related deaths occurred in the ADT plus docetaxel group (two of which were neutropenia-related), after which the data monitoring committee recommended treatment with granulocyte colony-stimulating factor. After this recommendation, no further treatment-related deaths occurred. No serious adverse events were reported in the ADT alone group. INTERPRETATION: Docetaxel should not be used as part of first-line treatment for patients with non-castrate metastatic prostate cancer. FUNDING: French Health Ministry and Institut National du Cancer (PHRC), Sanofi-Aventis, AstraZeneca, and Amgen.
The lancet oncology 01/2013; · 14.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: La curiethérapie par implants permanents est une alternative à la prostatectomie radicale ou à l’irradiation externe en cas
de cancer localisé de la prostate de bon pronostic. Les avantages de ce traitement sont une irradiation efficace mais précise,
limitée à la glande prostatique avec une morbidité modérée et passagère. Les troubles de l’érection fréquents après chirurgie
et irradiation externe sont retrouvés dans 6 à 61% des cas dans la littérature après curiethérapie. De tels écarts entre ces
taux sont liés aux différences en terme de suivi, de définitions des troubles sexuels, d’instruments de mesure utilisés. Ces
troubles de l’érection apparaissent entre 9 et 17 mois et seraient liés aux lésions radiques vasculaires des corps érectiles
proches de l’apex prostatique (bulbe urétral et base des corps caverneux). Cependant, la majorité des troubles de l’érection
répondent favorablement au traitements oraux tels que la yohimbine ou le sildénafil.
Parmi les options thérapeutiques à visée curative du cancer localisé de prostate, la curiethérapie par implants permanents
est le traitement qui préserve le mieux la fonction érectile.
Brachytherapy by permanent implants is an alternative to radical prostatectomy or external beam radiotherapy for good prognosis
localized prostate cancer. The advantages of this treatment are effective and precise irradiation, limited to the prostate
gland with moderate and transient morbidity. Erectile dysfunction, frequent erection after surgery and external beam radiotherapy,
is observed in 6% to 61% of cases in the literature after brachytherapy. This wide range is related to differences in terms
of follow-up, definition of sexual disorders, and the measuring instruments used. These erectile disorders occur between 9
and 17 months after treatment and appear to be related to vascular radiation lesions of the erectile bodies close to the prostatic
apex (urethral bulb and base of the corpora cavernosa). However, the majority of erectile disorders respond favourably to
oral treatments such as yohimbine or sildenafil.
Among the various curative treatment options for localized prostate cancer, permanent implant brachytherapy is the treatment
ensuring the best preservation of erectile function.
Andrologie 04/2012; 13(3):252-258.
-
[show abstract]
[hide abstract]
ABSTRACT: To validate the Briganti nomogram and compare it with 2 current lymph node invasion (LNI) nomograms (the Cagiannos nomogram and the updated 2007 Partin tables). The Briganti nomogram predicts the probability of LNI in patients undergoing extended pelvic lymph node dissection (EPLND) during radical prostatectomy for prostate cancer.
Irrespective of the risk of LNI, 173 consecutive patients were treated for localized prostate cancer with radical laparoscopic prostatectomy and EPLND. The area under the receiver operating characteristics curve was used to estimate the predictive accuracy of the nomograms, and calibration plots were used for comparisons between the predicted and observed probabilities of LNI.
The median number of nodes removed was 15 (range 10-34). Of the 173 patients, 12 (6.9%) had LNI. The Briganti nomogram achieved a receiver operating characteristic curve of 0.88 versus 0.83 with the Cagiannos nomogram and 0.84 with the 2007 Partin tables. The difference in predictive accuracy was not statistically significant (P < .2). The Briganti nomogram showed only minor departures from the ideal predictions in the low-risk range and the Cagiannos nomogram showed major departures from the ideal predictions for the entire risk range.
The Briganti nomogram provides highly accurate predictions of the risk of LNI after EPLND. Its performance tended to be increased without being significantly better. The other tools also performed reasonably well but underestimate the true risk of LNI. We recommend the use of these tools to identify patients at low risk of LNI for whom EPLND can be safely spared.
Urology 03/2012; 79(3):546-51. · 2.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: What's known on the subject? and What does the study add? Estramustine phosphate has anti-tumour properties and it improves patient outcomes if combined with other chemotherapy agents such as docetaxel. The efficacy of estramustine phosphate in selected patients and its safety profile, provided used with any low-molecular-weight heparin support its use as a second-line treatment in hormone-resistant prostate cancer.
• Estramustine phosphate is a nitrogen mustard derivative of estradiol-17β-phosphate and has anti-tumour properties. • Interest in estramustine has been renewed because of the results of clinical studies showing improved patient outcomes if estramustine is combined with other chemotherapy agents such as docetaxel.
• Relevant clinical studies using chemotherapy combinations including estramustine are discussed. • Efficacy and safety outcomes are summarized.
• Combination therapy with estramustine and docetaxel can increase PSA response rates, improve quality of life and increase median patient survival compared with chemotherapy regimens that do not include estramustine. • Although the overall tolerability of estramustine is favourable, its use can be associated with an increased risk of thromboembolic events.
• The identification of suitable patient groups and the effective management of the risk of thromboembolism with the adjunct of low-molecular-weight heparins support the use of estramustine as an effective second-line treatment strategy in hormone-resistant prostate cancer. • These promising findings warrant further investigation in a randomized clinical trial.
BJU International 07/2011; 108(11):1782-6. · 2.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Focal therapy of prostate cancer is gaining more and more interest. One of the drawbacks of focal therapy of prostate cancer is the problem of correct identification of prostate cancer lesions. The aim of the study was to evaluate the ability of real-time elastography to correctly identify the prostate cancer index lesion.
In 32 patients, real-time elastography was performed the day before prostatectomy. During the examination, the location of the main lesion suspicious for prostate cancer was prospectively recorded. Moreover, the results of the randomized multicore biopsies were also used to predict the location of the index lesion. The preoperative elastography results, the biopsy results, and a combined use of elastography and biopsy results were then compared with the pathological results to calculate the diagnostic values for correct index lesion identification.
When using real-time elastography alone to identify the prostate cancer index lesion, sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 58.8, 43.3, 54.1, 48.1, and 51.6%, respectively. Data from randomized biopsies alone achieved 67.8, 48.4, 56.8, 60.0, and 58.1%, respectively. The combination of elastography and biopsy data increased the values to, respectively, 84.9, 48.4, 61.9, 75.0, and 66.1%.
In this study, real-time elastography alone did not allow to identify the prostate cancer index lesion with satisfactory reliability. The combination of real-time elastography and data from randomized 12 core biopsies allows promising ability to correctly identify the prostate cancer index lesion.
World Journal of Urology 05/2011; 29(5):589-94. · 2.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Information is crucial for increasing the patients' empowerment and autonomy in relevant decision-making processes, especially in malignant diseases. However, the extent to which information should be delivered is debated. The objective of this study was to assess the impact of providing systematic full access (SFA) to the medical record on anxiety, quality of life, and satisfaction.
Patients with newly diagnosed breast cancer, colon cancer, or lymphoma who had received adjuvant chemotherapy in an outpatient setting were included in a randomized controlled trial comparing those who requested access (RA) and those who provided SFA to the medical record. Anxiety was assessed using the Spielberger State-Trait Anxiety Inventory before, during, and at the end of treatment. Quality of life was evaluated using the European Organization for Research and Cancer quality-of-life questionnaire (EORTC QLQ-C30) before and at the end of treatment. Patients' satisfaction and perception of the organized medical record (OMR) were evaluated using a specifically designed questionnaire at the end of treatment.
Most patients (98%) who had the opportunity to obtain the OMR chose to do so. Anxiety levels did not increase in the SFA arm, although they did not differ significantly compared with anxiety levels in the RA arm. The patients who had full access to their medical record were more satisfied with information (odds ratio, 1.68; 95% confidence interval, 0.98-2.9) and felt sufficiently informed more often (odds ratio, 1.86; 95% confidence interval, 1.08-3.19), but the differences were not statistically significant at the 5% level.
Allowing full access to personal medical records increased satisfaction without increasing anxiety in patients with newly diagnosed cancer. Cancer 2011;. © 2011 American Cancer Society.
Cancer 05/2011; 117(20):4796-804. · 4.77 Impact Factor
-
Jean-Christophe Eymard,
Stéphane Oudard, Gwenaelle Gravis,
Jean-Marc Ferrero,
Christine Theodore,
Florence Joly,
Frank Priou,
Ivan Krakowski,
Alain Zannetti,
Laurence Thill,
Philippe Beuzeboc
[show abstract]
[hide abstract]
ABSTRACT: To investigate the potential benefit of reintroducing docetaxel chemotherapy in patients with progressive metastatic castration-resistant prostate cancer (mCRPC) who had initially responded to first-line docetaxel-based regimen.
Records were evaluated retrospectively from French patients with mCRPC who had been included in seven controlled clinical studies of docetaxel as first-line treatment. We identified patients who were confirmed as responders to first-line treatment, discontinued for reasons other than disease progression or unacceptable toxicity, and who received further docetaxel chemotherapy for disease progression. The primary objective was to assess efficacy in terms of the prostate-specific antigen (PSA) response after resuming a docetaxel-based chemotherapy. Secondary objectives were overall survival and tolerance.
Of the 148 patients who responded to first-line docetaxel, 50 received further therapy with docetaxel and were analysed. The median (range) response duration to first-line docetaxel was 10.3 (4.6-45.7) months and the median docetaxel-free interval was 18.4 (5.0-46.7) months. Docetaxel was reintroduced as second-line therapy in 52% of patients and as further lines in 48%. After docetaxel reintroduction, 24 patients (48%) had a 50% decrease in PSA level (95% confidence interval, CI, 34.1-61.8%). The median (95% CI) overall survival from docetaxel reintroduction was 16 (13-20) months. Re-treatment was well tolerated (6% of grade 3-4 haemotoxicity).
Docetaxel reintroduction appears to be effective, with favourable tolerance profiles, in patients with mCRPC having responded to first-line docetaxel, and should be prospectively assessed in clinical trials against alternative therapies or investigational agents given alone or in combination, to define further management.
BJU International 03/2010; 106(7):974-8. · 2.84 Impact Factor
-
Sylvie Négrier,
David Perol,
Alain Ravaud,
Jacques O Bay,
Stéphane Oudard,
Sylvie Chabaud,
Pierre Fargeot,
Remy Delva,
Gael Deplanque, Gwenaelle Gravis,
Bernard Escudier
[show abstract]
[hide abstract]
ABSTRACT: Metastatic renal cancer patients with a single metastatic site are potentially amenable to interleukin 2 (IL-2) + IFN-alpha. A French immunotherapy intergroup multicenter trial assessed the potential benefit of i.v. over s.c. administration of IL-2 in this combination.
Untreated patients with one metastatic site were randomized to continuous i.v. infusion (18 x 10(6) IU/m(2)/d; arm A) or twice daily s.c. injections (9 x 10(6) or 18 x 10(6) IU; arm B) of IL-2, associated with s.c. IFN-alpha (6 x 10(6) IU) 3 days per week in both arms. Tumor response was assessed (WHO criteria) at weeks 12 and 24 to 26. The primary end point was overall survival, with an expected 15% improvement at 4 years with i.v. IL-2. The planned sample size was 220 (80% power, 5% significance, one-sided test). Intent-to-treat analysis was done and survivals were compared using log-rank tests.
From January 2000 to January 2005, 80 and 75 patients were randomized to arms A and B, respectively. Enrollment was stopped early because of low accrual; analysis was done at 42.5 months median follow-up. Patient characteristics were well balanced between groups. Response rates were 17.9% versus 21.3% in arms A and B. Progression-free survival rates were not significantly different. Overall survival difference was not significant: median 33 months (95% confidence interval, 27.0-40.2; P = 0.202).
In combination with IFN-alpha in selected, good prognosis metastatic renal cell carcinoma patients, i.v. IL-2 offers no significant advantage over s.c. IL-2 and induces higher toxicity. Although i.v. IL-2 induced longer responses, it seems unreasonable to continue recommending this regimen after the recent introduction of more effective therapies.
Clinical Cancer Research 10/2008; 14(18):5907-12. · 7.74 Impact Factor
-
Tim Eisen,
Stéphane Oudard,
Cezary Szczylik, Gwenaelle Gravis,
Hans Heinzer,
Richard Middleton,
Frank Cihon,
Sibyl Anderson,
Sonalee Shah,
Ronald Bukowski,
Bernard Escudier
[show abstract]
[hide abstract]
ABSTRACT: The perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials and the known toxic effects of cytotoxic chemotherapy. It is not known how older patients respond to targeted therapy.
This retrospective subgroup analysis of data from the phase 3, randomized Treatment Approach in Renal Cancer Global Evaluation Trial examined the safety and efficacy of sorafenib in older (age >or=70 years, n = 115) and younger patients (age <70 years, n = 787) who received treatment for advanced renal cell carcinoma. Patient demographics and progression-free survival were recorded. Best tumor response, clinical benefit rate (defined as complete response plus partial response plus stable disease), time to self-reported health status deterioration, and toxic effects were assessed by descriptive statistics. Health-related quality of life was assessed with a Cox proportional hazards model. Kaplan-Meier analyses were used to summarize time-to-event data.
Median progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks; hazard ratio [HR] for progression compared with placebo = 0.55, 95% confidence interval [CI] = 0.47 to 0.66) and older patients (26.3 weeks; HR = 0.43, 95% CI = 0.26 to 0.69). Clinical benefit rates among younger and older sorafenib-treated patients were also similar (83.5% and 84.3%, respectively) and were superior to those of younger and older placebo-treated patients (53.8% and 62.2%, respectively). Adverse events were predictable and manageable regardless of age. Sorafenib treatment delayed the time to self-reported health status deterioration among both older patients (121 days with sorafenib vs 85 days with placebo; HR = 0.66, 95% CI = 0.43 to 1.03) and younger patients (90 days with sorafenib vs 52 days with placebo; HR = 0.69, 95% CI = 0.59 to 0.81) and improved quality of life over that time.
Among patients with advanced renal cell carcinoma receiving sorafenib treatment, outcomes of older (>or=70 years) and younger (<70 years) patients were similar.
CancerSpectrum Knowledge Environment 10/2008; 100(20):1454-63. · 14.07 Impact Factor
-
ASCOASCO, Chicago, Illinois; 01/2008
-
[show abstract]
[hide abstract]
ABSTRACT: Medullary thyroid carcinoma with distant metastases is generally incurable, with 20% overall survival at 10 years. The treatment goal is palliative. Chemotherapy has a limited role, with low response rates and high toxicities with the different regimens. Here, we report the case of 64-year-old man with metastatic medullary thyroid carcinoma in progression after primary treatment with cisplatin-doxorubicin. The patient received capecitabine 2000 mg/m total per day x 14 days followed by 1-week rest. He received 41 cycles, and presented prolonged and objective tumor response (30 months), without any toxicity.
Anti-Cancer Drugs 09/2007; 18(7):831-4. · 2.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Androgen deprivation in patients with metastatic prostate cancer produces palliation of symptoms, PSA decrease and tumoral regression in most patients. After a brief period of disease regression lasting 18 to 24 months nearly all pts will progress to androgen independence disease (HRPC) with progressive clinical deterioration and ultimately death. Chemotherapy with mitoxantrone has been shown to palliate symptoms but did not extend survival. Two large randomized trials showed a survival benefit for pts with HRPC treated with docetaxel with a reduction risk of death by 21-24%, and significant improvement in palliation of symptoms and quality of life. New agents targeting angiogenesis, apoptosis, signal transduction pathway, used alone or in combination with docetaxel currently are under trial in an attempt to provide much needed improvements in outcome. Questions remains in suspend when and who need to be treated, earlier, in high risk as in adjuvant setting? Current data have demonstrated that neoadjuvant or adjuvant chemotherapy is relatively safe and feasible. Further investigation through prospective randomize trials is critical to define the precise role of this modality in high risk populations.
Bulletin du cancer 08/2007; 94(7 Suppl):F21-8. · 0.67 Impact Factor
-
Ferran Guedea,
Ferran Aguilo,
Alfredo Polo,
Stephen Langley,
Robert Laing,
Alastair Henderson,
Sirpa Aaltomaa,
Vesa Kataja,
Juni Palmgren,
Franch Bladou,
Naji Salem, Gwenaelle Gravis,
Andrea Losa,
Giorgio Guazzoni,
Luciano Nava
[show abstract]
[hide abstract]
ABSTRACT: Five European centres (France, Finland, Italy, Spain and the UK) have pooled data to generate a large patient series involving 1175 patients treated with prostate brachytherapy. This paper reports preliminary data on PSA outcome up to 4 years.
Out of 1175 in the database, 1050 patients with localised prostate cancer who had received transperineal seed implantation as monotherapy between May 1998 and August 2003 were stage T1-T2. A total of 668 (63.6%) patients met the low-risk group definition, 297 (28.3%) as intermediate-risk definition and 66 (6.3%) the high-risk group definition. The majority of patients were Gleason score 6 or less (n=951) and disease stage was T1c in 557 patients.
Of the 1050 patients, PSA data up to 4 years were available for 210 patients, while 364 patients with PSA values up to 36 months were evaluable by the Kaplan-Meier method for freedom from biochemical failure. The biochemical progression-free rate at 3 years was estimated to be 91%, with a 93% and 88% rate for low- and intermediate-risk groups, respectively, versus 80% for the high-risk group. PSA kinetics provide encouraging evidence of treatment efficacy.
These data on 4-year PSA follow-up on patients treated with prostate brachytherapy reflect those previously reported in the literature. This patient series will be followed to provide long-term outcome in the future.
Radiotherapy and Oncology 08/2006; 80(1):57-61. · 5.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study investigated the role of inflammatory cytokines in acute graft-versus-host disease (aGVHD) incidence and severity in 113 patients who underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT). Among all tested cytokines in the first 3 months after allo-SCT, only interleukin-12 p70 (IL-12p70) levels in the first month were significantly associated with grades II to IV aGVHD development (P < .001). IL-12p70 levels were directly correlated with aGVHD severity grade (P < .001). Before aGVHD onset, blood monocytes, the main precursor pool of IL12p70-secreting dendritic cells, recovered more rapidly in patients with grades II to IV aGVHD (P = .005). Similarly, at the effector level, there was a more robust reconstitution of naive CD3+CD4+CD45RA+CD27+ T cells in patients developing grades II to IV aGVHD (P = .006). In multivariate analysis, IL-12p70 level measured in the first month was the strongest predictive factor for aGVHD development (P < .001). These findings, reconstituting a T(H)1 loop, support a model in which aGVHD reflects a type 1 alloreaction after RIC allo-SCT.
Blood 01/2006; 106(13):4407-11. · 9.90 Impact Factor
-
ASCO Prostate Cancer SymposiumASCO Prostate Cancer Symposium, San Francisco, California; 01/2006
-
[show abstract]
[hide abstract]
ABSTRACT: To describe the outcome of patients with muscle-invasive bladder carcinoma treated with multimodality therapy in our institution from 1993 to 2002.
The charts of 60 patients with Stage T2-T4N0-N1M0 treated with transurethral resection of bladder tumor followed by a chemoradiotherapy combination were retrospectively reviewed. Of the 60 patients, 22 had received neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine or methotrexate, adriamycin, cisplatin, and vinblastine) followed by concomitant chemoradiotherapy (weekly cisplatin/carboplatin or a cisplatin and 5-fluorouracil combination), and 38 had received concomitant chemoradiotherapy alone. Radiotherapy delivered a median dose of 45 Gy to the pelvis and 65 Gy to the bladder in a once-daily or twice-daily fractionation scheme. Follow-up evaluations included cystoscopy with biopsies at regular intervals. Salvage cystectomy was recommended in the case of local persistent tumor or bladder relapse.
The median follow-up was 48.5 months (range 10 to 126). Of the 22 patients who received neoadjuvant chemotherapy, 18 (82%) had received two or more cycles; 51 (85%) of the 60 patients received the concomitant chemotherapy as planned. Radiotherapy was completed in 56 patients. Twenty-eight patients developed relapse either locally (14 did not achieve a complete local response after chemoradiotherapy and 6 had true local relapse during follow-up) or at distant sites. The actuarial 5-year disease-specific survival and freedom from local and distant relapse rate was 54% and 42%, respectively. The actuarial local control rate with an intact bladder was 56% at 5 years. When stratified according to stage and grade, patients with Stage T2-T3, grade 2 tumors had a statistically significantly better chance of remaining relapse free than did the others (P = 0.045). Salvage cystectomy (n = 11) for isolated local failure in this population achieved limited results.
Transurethral resection of bladder tumor with this chemoradiotherapy combination achieved satisfactory results in this unfavorable population with invasive bladder carcinoma.
Urology 10/2004; 64(3):488-93. · 2.43 Impact Factor
-
Didier Blaise,
Jacques Olivier Bay,
Catherine Faucher,
Mauricette Michallet,
Jean-Michel Boiron,
Bachra Choufi,
Jean-Yves Cahn,
Nicole Gratecos,
Jean-Jacques Sotto,
Sylvie François,
Joel Fleury,
Mohamad Mohty,
Christian Chabannon,
Karin Bilger, Gwenaelle Gravis,
Frédéric Viret,
Anne Chantal Braud,
Valérie Jeanne Bardou,
Dominique Maraninchi,
Patrice Viens
[show abstract]
[hide abstract]
ABSTRACT: In this prospective multicenter program, we investigated allogeneic stem cell transplantation (ASCT) from HLA-identical siblings following reduced-intensity conditioning (RIC) regimen for patients with refractory metastatic solid tumors (STs). Fifty-seven patients, of whom 39 had a progressive disease (PD) at time of ASCT, received an RIC ASCT combining fludarabine, antithymocyte globulin (ATG), and busulfan. Patients were analyzed in terms of engraftment, transplant-related mortality (TRM), disease response, and outcome. In this setting, RIC was associated with rapid engraftment and low overall TRM (9% [95% confidence interval (CI), 1%-16%]). The cumulative incidence of objective responses (ORs) reached 14% (95% CI, 6%-30%) with this being significantly higher in patients without PD (44% [95% CI, 21%-67%] versus 0; P <.0001) at time of ASCT. Achievement of OR translated into a significantly better overall survival (OS). In multivariate analysis, OS was significantly influenced by disease status at time of ASCT (odds ratio, 4.88; P <.001) and chronic graft-versus-host disease (GVHD) occurrence (odds ratio, 2.86; P <.01). Overall, these results showed that OR can occur after RIC ASCT for resistant ST with a relatively low TRM and potential benefit especially in patients with slowly progressive disease. Further studies are warranted in patients with less advanced ST.
Blood 01/2004; 103(2):435-41. · 9.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The current Phase II study investigated the clinical benefit, impact on quality of life (QOL), and tolerability of weekly docetaxel in symptomatic patients with metastatic hormone-refractory prostate carcinoma (HRPC).
Patients received weekly docetaxel 35 mg/m(2) intravenously for 6 consecutive weeks followed by a 2-week rest repeatedly for a maximum of 24 weeks of treatment. Clinical benefit evaluations, based on Karnofsky performance status (KPS) and pain, were assessed weekly during therapy. A clinical benefit response was defined as a sustained (> or = 4-week) improvement in at least one of these parameters without worsening in the other. Patient-assessed QOL (using the European Organization for Research and Treatment of Cancer QLQ-C30), changes in prostate-specific antigen (PSA) levels, tumoral response, and toxicity also were evaluated.
Thirty men (median age, 67 years), 15 of whom had received previous chemotherapy, were treated. Overall, 46% of patients achieved a positive pain response and 48% achieved a 50%-or-greater reduction in PSA. KPS was high at baseline (80%), and no significant changes in this parameter were observed. Compared with baseline, all scores improved after the first cycle of therapy, particularly emotional (P = 0.015), pain (P = 0.001), constipation (P = 0.001), and global QOL (P = 0.011) scores. After the second cycle, dyspnea scores decreased (P = 0.010). At the last QOL assessment, there also was deterioration in terms of fatigue (P = 0.013), dyspnea (P = 0.010), and physical functioning (P = 0.017). Toxicity was mild and included neutropenia (Grade 3-4, n = 2).
Of these elderly symptomatic patients with HRPC, half had received previous chemotherapy. Weekly docetaxel was found to be associated with improvements in clinical benefit response and in QOL and was well tolerated.
Cancer 10/2003; 98(8):1627-34. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To analyse predictive factors of acute urinary morbidity after transperineal permanent prostate brachytherapy.
Sixty patients treated in a phase 2 study with iodine-125 brachytherapy (9/1998 to 2/2000) for localised prostate adenocarcinoma were analysed after at least 1-year follow-up. Prescribed dose was 144 Gy and all patients had a pre-planning and a post-implant dosimetry. Urinary morbidity was evaluated prospectively using the Radiation Therapy Oncology Group (RTOG) scale. We examined the relationship between pre-implant ultrasound prostate volume, post-implant CT-scan prostate volume, neoadjuvant hormonotherapy, total number of needles and seeds, post-implant dosimetry variables, first 30 vs. last 30 treated patients and post-implant urinary morbidity.
All patients experienced some degree of urinary distress symptoms after treatment. Symptoms were generally mild grade 1 in 56% and grade 2 in 10% lasting less than 6 months. Eight patients (13%) required bladder catheter for acute urinary obstruction. At 1-year follow-up, nine patients (15%) complained from persistent dysuria requiring in three cases endoscopic prostate resection. The percentage of urethra volume receiving 216 Gy (cut-off 40%) and the pre-implant prostate volume (cut-off 31 ml) were the only statistically significant predictor of grade 2-3 or persistent urinary morbidity on multivariate analysis.
Our short-term data suggest that both pre-implant prostate volume value and post-implant V.U. 150 value might be predictors for urinary morbidity after prostate brachytherapy.
Radiotherapy and Oncology 03/2003; 66(2):159-65. · 5.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of our study was to assess the feasibility, toxicity, and pharmacokinetics of an escalating dose of docetaxel when administered with granulocyte colony-stimulating factor (G-CSF) support every 3 weeks.
Patients with advanced solid malignancies were treated with escalating doses of docetaxel as a 1-h infusion every 3 weeks, supported by s.c. administration of human recombinant glycosilated G-CSF Granocyte (lenograstim), 5 microg/kg/day (from day 4 until neutrophil count >0.5-10(g)/liter for two consecutive days). Plasma sampling was performed to characterize the pharmacokinetics of docetaxel at the new recommended high-dose level.
Forty-seven patients were treated with 116 courses of docetaxel at eight dose levels ranging from 100-185 mg/m(2). Dose-limiting toxicities were nonhematologic and included mucositis and dermatitis. Severe skin toxicity observed at 185 mg/m(2) led to discontinuing the study, and 175 mg/m(2) was selected as the recommended dose of docetaxel + G-CSF for future Phase II studies. Analysis of multiple courses revealed dermatitis, mucositis, arthralgia/myalgia, and neuropathy as the main dose-related toxic events. At 175 mg/m(2) mean +/- SD values for docetaxel plasmatic peak, area under the curve, clearance, volume of distribution, and terminal half-life were 6.7 +/- 1.7 microg/ml, 9.7 +/- 4 microg.h/ml, 34.2 +/- 12 liters/h, and 122.7 +/- 124 liters, respectively. Of the 16 patients treated at 175 mg/m(2), 8 patients responded (7 breast cancer and 1 lung cancer patients) including one complete response (1 breast cancer patient).
Using G-CSF support allows substantial dose escalation of docetaxel. Whether such a dose increase improves the response rate warrants further investigation. At the highest dose level studied, pharmacokinetic parameters seem to maintain a linear profile.
Clinical Cancer Research 01/2003; 9(1):102-8. · 7.74 Impact Factor
