Mario Di Palma

Phase II Trial of Consolidation Docetaxel and Samarium-153 in Patients With Bone Metastases From Castration-Resistant Prostate Cancer

PURPOSE To assess docetaxel combined with samarium-153-ethylene diamine tetramethylene phosphonic acid (EDTMP), a radiopharmaceutical with a high affinity for bone, in patients with castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS Patients with bone metastases from CRPC who achieved a response or stabilization after four cycles of docetaxel and estramustine were given consolidation docetaxel 20 mg/m(2)/wk for 6 weeks and samarium-153-EDTMP (37 MBq/kg) during week 1. Prostate-specific antigen (PSA) response was assessed by using consensus criteria, and pain was assessed by using a visual analog scale (VAS). This study used a Simon two-step design with PSA-progression-free survival (PFS) as the primary end point. RESULTS Forty-three patients were included in the trial. A PSA response was obtained in 77% (95% CI, 61% to 82%). The pain response rate was 69% (95% CI, 49% to 85%). At least five of the six planned weekly injections of docetaxel were administered to 34 patients (81%). The consolidation docetaxel-samarium-153-EDTMP regimen was well tolerated; there was no febrile neutropenia, and only two episodes (5%) of rapidly reversible grade 3 thrombocytopenia occurred. Although a serum PSA relapse eventually occurred in all patient cases, this regimen resulted in pain control in the long-term. The median PSA-PFS was 6.4 months (95% CI, 6 to 7 months). The median survival was 29 months (95% CI, 22 to 31); the 1-year survival rate was 77% (62% to 87%); and the 2-year survival rate was 56% (41% to 70%). CONCLUSION Combining docetaxel and samarium-153-EDTMP in patients with bone metastases from CRPC is well tolerated, and it yields major pain relief that persists long after treatment. Overall survival compares favorably with that expected in this population of patients, most of whom exhibit symptoms.

Quality of Life of Patients Operated on for Low Rectal Cancer: Impact of the Type of Surgery and Patients’ Characteristics

PURPOSEThis study was designed to compare the impact of a permanent colostomy and sociodemographic characteristics on the quality of life of patients operated on for low rectal cancer.METHODSA cross-sectional study was performed by use of the European Organization for Research and Treatment of Cancer QLQ-C30 and CR-38 questionnaires. Patients came to the hospital to fill out the self-administered questionnaire or were sent the questionnaire by mail, followed by a live or telephone interview. All patients had undergone one of four operations: low anterior resection with colorectal or coloanal anastomosis (non-stoma group), or abdominoperineal resection with pseudocontinent perineal colostomy (nonstoma group) or left lower quadrant colostomy (stoma group).RESULTSA total of 132 patients were included for analysis and there were no missing data. For the majority of quality of life scores (26/29), there was no significant difference between stoma and nonstoma patients. However, stoma patients complained of diminished body image (P = 0.0022), and this was especially true for married (P = 0.0073) and less educated (P = 0.0014) patients at subgroup analysis. Stoma patients experienced greater financial worries (P = 0.0029), whereas nonstoma patients had greater gastrointestinal concerns (P = 0.0098).CONCLUSIONSAlthough most quality of life scores between stoma and nonstoma patients were similar, significant differences regarding body image, finance, and gastrointestinal symptoms, especially for married and less educated patients, were noticed. These factors should be taken into account, along with oncologic criteria, to better tailor treatments to patients.

Skeletal muscle density predicts prognosis in patients with metastatic renal cell carcinoma treated with targeted therapies

Studies have shown that skeletal muscle and adipose tissue are linked to overall survival (OS) and progression‐free survival (PFS). Because targeted therapies have improved the outcome in patients with metastatic renal cell carcinoma (mRCC), new prognostic parameters are required. The objective of the current study was to analyze whether body composition parameters play a prognostic role in patients with mRCC.

The interval from the last cycle of docetaxel-based chemotherapy to progression is associated with the efficacy of subsequent docetaxel in patients with prostate cancer

There is currently no standard treatment after first-line docetaxel-based chemotherapy for patients with castration-refractory prostate cancer (CRPC). Some patients are likely to discontinue first-line docetaxel-based chemotherapy because of either completed treatment or the occurrence of manageable side-effects. The aim of this study was to determine whether a rechallenge with docetaxel might be appropriate in patients with CRPC previously treated with docetaxel. Between December 2004 and July 2009, 39 patients diagnosed with metastatic cancer prostate at the Institut Gustave Roussy were administered subsequent docetaxel after front-line docetaxel-based chemotherapy. The medical records of these patients were extracted from the database. The PSA response rate (PSA decline > or =30% and > or =50%), progression-free survival (PFS) and overall survival (OS) of patients receiving docetaxel as a subsequent line of therapy were evaluated using consensus criteria. The effect of pre-treatment variables on efficacy was studied. A PSA decline > or =30% and > or =50% was observed in 64% and 38% of patients, respectively, median PFS was 4.3 months [confidence interval (CI) 95%: 3.6-4.9] and median OS was 15.8 months (CI 95%: 11.7-20.3) in 39 patients who received subsequent docetaxel. The interval between the last cycle of first-line docetaxel and progression [median: 3.0 months; range: 1-30 months] was associated with PFS: median PFS was 3.4 months (CI 95%: 2.6-4.1) and 6.3 months (CI 95%: 3.0-5.6), respectively, in patients with an interval <3.0 months and an interval > or =3.0 months, (p=0.04). Tolerance of re-treatment with docetaxel was acceptable with no toxicity-related death. Re-treatment with subsequent docetaxel in patients with CRPC pretreated with first-line docetaxel is safe and demonstrates some activity. The interval from the last cycle of first-line docetaxel-based chemotherapy to progression is associated with the efficacy of subsequent docetaxel.

‘Burned‐out’ primary testicular cancer

To report the natural history of ‘burned‐out’ testicular tumour (a testicular tumour that has regressed spontaneously with no treatment and that generally presents at the stage of metastases).

Systematic review of amifostine for the management of oral mucositis in cancer patients

PurposeThe aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the prevention and treatment of oral mucositis in cancer patients.MethodsA systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for the use of amifostine, in each cancer treatment setting was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible.ResultsThirty papers were reviewed for evidence on amifostine as an intervention for oral mucositis. No guideline was possible for amifostine in any cancer treatment setting due to inadequate and conflicting evidence.ConclusionReview of the amifostine studies for the prevention and treatment of oral mucositis has found insufficient evidence to support its use in any cancer treatment setting for this purpose. Additional well-designed research is needed to clarify the role of amifostine as an intervention for oral mucositis.

Personalizing treatment in patients with castrate-resistant prostate cancer: A study of predictive factors for secondary endocrine therapies activity.

213 Background: Several options have recently demonstrated activity, including survival improvement, in patients with prostate cancer progressing while on androgen deprivation therapy: chemotherapy (docetaxel, cabazitaxel), sipuleucel-T, and abiraterone. There is now an urgent need to identify predictive factors of efficacy for each of these treatments to assist decision-making in pts with castrate-resistant prostate cancer (CRPC). We attempted to identify predictive factors for activity of subsequent endocrine manipulations in patients with CRPC. METHODS Patients with CRPC included in the Institut Gustave Roussy clinical trials database who received endocrine manipulations (abiraterone, ketoconazole-hydrocortisone, DES, bicalutamide) for CRPC were reviewed. The predictive role on response and progression-free survival (PFS) of a series of clinical, biological, and radiological parameters was studied (Khi-2 test for response, Logrank test and Cox model for PFS). RESULTS 108 patients with CRPC who participated to 5 clinical trials were identified. The median duration of prostate cancer sensitivity to ADT (defined as the time from ADT initiation to the outset of castrate-resistance) was 16 months (range: 0-118 months). Timing of endocrine manipulation (before vs after docetaxel-based chemotherapy), presence of non-bone visceral metastases, the type of progression (clinical vs radiological), Performance Status, and PSA doubling time did not predict for response or PFS. In contrast, the previous duration of prostate cancer sensitivity to ADT (classified as ≥16 months and <16 months) significantly and strongly predicted for both PSA response (58% vs 18%, p=0.01) and PFS (median PFS rates: 5 months (95%CI: 3.46-6.53) and 3 months (95%CI: 2.10-3.89) p<0.043). CONCLUSIONS A previous duration of prostate cancer sensitivity to ADT ≥16 months is the only significant predictive factor for efficacy of subsequent endocrine manipulations in patients with CRPC. This parameter shall be integrated into the decision-making process for these patients.

Gemcitabine in Patients With Solid Tumors and Renal Impairment: A Pharmacokinetic Phase I Study

The purpose of this phase I study was to determine the pharmacokinetics and toxicity of gemcitabine in patients with advanced, recurrent, and/or metastatic cancer and renal impairment. Patients were entered in 4 groups estimated by EDTA-Cr51 plasma clearance (CLp, mL/min): ≥80; ≥60 and <80; ≥30 and <60; and ≥30 and <80 plus renal insufficiency induced by previous chemotherapy, respectively. Gemcitabine 500 to 1000 mg/m2 was administered intravenously on days 1, 8, and 15 every 4 weeks. Plasma concentration data were pooled and analyzed using a population pharmacokinetic program (NONMEM). Eighteen white patients (14 females, 4 males) entered the study with a median age of 55 years. Linear regression analyses revealed no significant relationship between gemcitabine CLp and indices of renal impairment (EDTA-Cr51 CL; p = 0.797 or β2-microglobulin; p = 0.153). Hematologic and nonhematologic toxicities were mild. Thus, there seems to be no significant impact of mild to moderate renal insufficiency on gemcitabine pharmacokinetics in patients with advanced cancer.

Axillary Padding without Drainage after Axillary Lymphadenectomy – a Prospective Study of 299 Patients with Early Breast Cancer

Background: After lymphadenectomy for early breast cancer, seroma formation is a constant event requiring a suction drainage. This drainage is the strongest obstacle to reducing the hospital stay. Axillary padding without drainage appears to be a valuable option amid the various solutions for reducing the hospital stay. Methods: We conducted a comparison between 114 patients with padding and 185 patients with drainage. Data were obtained from 2 successive prospective studies. Results: The mean hospital stay was 2.4 days (range 1–4) in the padding group and 4.2 days (range 2–9) in the drainage group (p < 0.05). There were fewer needle aspirations for seroma in the padding group (8.8 vs. 23%, p < 0.05). At 6 weeks, only 28% (32/114) of the patients in the padding group reported pain versus 51% (94/185) in the drainage group. The mean pain intensity at 6 weeks was 3 and 4.3 respectively (p < 0.0001). Conclusion: Axillary padding without drainage was associated with a better post-operative course than suction drainage in this historical comparison, and the hospital stay was significantly shortened. There are only few series published on this new technique but they all indicate good feasibility and good tolerance. A large randomised multicentric evaluation is now warranted.

Évaluation et caractéristiques des accès douloureux paroxystiques chez les patients souffrant de douleurs d’origine cancéreuse

Resume Les acces douloureux paroxystiques sont definis comme crises douloureuses transitoires, survenant dans un contexte de douleur chronique. Le but de cette etude etait d’evaluer de facon prospective ces acces douloureux paroxystiques chez des patients souffrant de douleurs d’origine cancereuse, traites par des doses stables d’opioides. Il a ete demande a ces patients de remplir un carnet de bord pendant une semaine, de preciser en cas de crise douloureuse l’heure de debut, la duree, l’intensite, le recours a un traitement specifique et son efficacite eventuelle. Au total, 183 patients evaluables ont ete inclus qui ont rapporte 1 405 episodes d’acces douloureux paroxystiques. Pour 81 % des patients, il existait au moins un episode douloureux pendant la semaine de suivi de l’etude. Pour ces patients, le nombre moyen d’acces douloureux etait de 1,35 par jour, le nombre moyen de jours avec au moins un acces douloureux etait de 3,8 pour la semaine de l’etude. Un tiers des patients s’est plaint d’acces douloureux tous les jours. L’intensite des douleurs pendant la crise etait notee severe ou intolerable dans la moitie des cas. Le traitement specifique a prendre en cas d’acces douloureux etait prevu pour l’ensemble des patients, mais 26 % des episodes douloureux n’etaient pas traites, et lorsqu’un traitement etait pris, le traitement etait considere comme inefficace dans un tiers des cas. Il est evident que des traitements specifiques des acces douloureux sont necessaires afin de permettre une meilleure prise en compte de ce probleme.