RÉSUMÉ
BACKGROUND: Reliable and affordable prognostic and predictive biomarkers for urothelial carcinoma treated with immunotherapy may allow patients' outcome stratification and drive therapeutic options. The SAUL trial investigated the safety and efficacy of atezolizumab in a real-world setting on 1004 patients with locally advanced or metastatic urothelial carcinoma who progressed to one to three prior systemic therapies. PATIENTS AND METHODS: Using the SAUL Italian cohort of 267 patients, we investigated the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) and the best performing one of these in combination with programmed death-ligand 1 (PD-L1) with or without lactate dehydrogenase (LDH). Previously reported cut-offs (NLR >3 and NLR >5; SII >1375) in addition to study-defined ones derived from receiver operating characteristic (ROC) analysis were used. RESULTS: The cut-off values for NLR and SII by the ROC analysis were 3.65 (sensitivity 60.4; specificity 63.0) and 884 (sensitivity 64.4; specificity 67.5), respectively. The median overall survival (OS) was 14.7 months for NLR <3.65 [95% confidence interval (CI) 9.9-not reached (NR)] versus 6.0 months for NLR ≥3.65 (95% CI 3.9-9.4); 14.7 months for SII <884 (95% CI 10.6-NR) versus 6.0 months for SII ≥884 (95% CI 3.7-8.6). The combination of SII, PD-L1, and LDH stratified OS better than SII plus PD-L1 through better identification of patients with intermediate prognosis (77% versus 48%, respectively). Multivariate analyses confirmed significant correlations with OS and progression-free survival for both the SII + PD-L1 + LDH and SII + PD-L1 combinations. CONCLUSION: The combination of immune-inflammatory biomarkers based on SII, PD-L1, with or without LDH is a potentially useful and easy-to-assess prognostic tool deserving validation to identify patients who may benefit from immunotherapy alone or alternative therapies.
Sujet(s)
Carcinome transitionnel , Tumeurs du poumon , Tumeurs de la vessie urinaire , Tumeurs urologiques , Marqueurs biologiques , Humains , Immunothérapie , Italie , Pronostic , Tumeurs urologiques/diagnostic , Tumeurs urologiques/thérapieRÉSUMÉ
OBJECTIVE: Hypersensitivity reactions (HSR) are frequently reported in patients rechallenged with carboplatin for recurrent ovarian cancer (ROC) and represent a critical issue, since discontinuation of the platinum-based therapy could affect prognosis. Several strategies to allow platinum rechallenge have been described, with controversial outcomes. The aim of this study is to illustrate a 10-year experience with cisplatin in patients with a previous HSR to carboplatin or at risk for allergy. METHODS: A retrospective review of all patients with platinum sensitive ROC retreated with carboplatin was performed between January 2007 and May 2016 at the Istituto Nazionale Tumori, Fondazione "G. Pascale", Naples. RESULTS: Among 183 patients, 49 (26.8%) presented HSR to carboplatin, mainly during second line therapy. Mean number of cycles before HSR was 8 (range 3-17). G2, G3 and G4 reaction were detected in 83%, 15% and 2% of patients, respectively. In a multivariate analysis including age, hystotype, BRCA status, previous known HSR, and combination drug administered, only the type of carboplatin-based doublet used as 2nd line therapy was found to significantly affect HSR development, with a protective effect of PLD (pegylated liposomal doxorubicin) (p = 0.014, OR = 0.027). Thirty seven patients (77%) with a previous HSR to carboplatin were rechallenged with cisplatin. Treatment was generally well tolerated. 5 patients (13.1%) experienced mild HSR to cisplatin, successfully managed in all cases. 14 patients were treated with cisplatin even without a carboplatin-related HSR due to other allergies. Among these, only one developed HSR (7.1%). CONCLUSIONS: Cisplatin rechallenge is a feasible approach in patients experiencing HSR to carboplatin to maintain the beneficial effect of platinum while reducing hypersensitivity-related risks.
Sujet(s)
Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Carboplatine/effets indésirables , Cisplatine/administration et posologie , Hypersensibilité médicamenteuse/étiologie , Récidive tumorale locale/traitement médicamenteux , Tumeurs de l'ovaire/traitement médicamenteux , Sujet âgé , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Carboplatine/administration et posologie , Carboplatine/immunologie , Cisplatine/effets indésirables , Désoxycytidine/administration et posologie , Désoxycytidine/analogues et dérivés , Doxorubicine/administration et posologie , Doxorubicine/analogues et dérivés , Femelle , Humains , Adulte d'âge moyen , Paclitaxel/administration et posologie , Polyéthylène glycols/administration et posologie , Études rétrospectives ,RÉSUMÉ
BACKGROUND: Platinum-based systemic chemotherapy is considered the backbone for management of advanced urothelial carcinomas. However there is a lack of real world data on the use of such chemotherapy regimens, on patient profiles and on management after treatment failure. METHODS: Fifty-one randomly selected physicians from 4 European countries registered 218 consecutive patients in progression or relapse following a first platinum-based chemotherapy. Patient characteristics, tumor history and treatment regimens, as well as the considerations of physicians on the management of urothelial carcinoma were recorded. RESULTS: A systemic platinum-based regimen had been administered as the initial chemotherapy in 216 patients: 15 in the neoadjuvant setting, 61 in adjuvant therapy conditions, 137 in first-line advanced setting and 3 in other conditions. Of these patients, 76 (35 %) were initially considered as cisplatin-unfit, mainly because of renal impairment (52 patients). After platinum failure, renal impairment was observed in 44 % of patients, ECOG Performance Status ≥ 2 in 17 %, hemoglobinemia < 10 g/dL in 16 %, hepatic metastases in 13 %. 80 % of these patients received further anticancer therapy. Immediately after failure of adjuvant/neoadjuvant chemotherapy, most subsequent anticancer treatments were chemotherapy doublets (35/58), whereas after therapy failure in the advanced setting most patients receiving further anticancer drugs were treated with a single agent (80/114). After first progression to chemotherapy, treatment decisions were mainly driven by Performance Status and prior response to chemotherapy (>30 % patients). The most frequent all-settings second anticancer therapy regimen was vinflunine (70 % of single-agent and 42 % of all subsequent treatments), the main reasons evoked by physicians (>1 out of 4) being survival benefit, safety and phase III evidence. CONCLUSION: In this daily practice experience, a majority of patients with urothelial carcinoma previously treated with a platinum-based therapy received a second chemotherapy regimen, most often a single agent after an initial chemotherapy in the advanced setting and preferably a cytotoxic combination after a neoadjuvant or adjuvant chemotherapy. Performance Status and prior response to chemotherapy were the main drivers of further treatment decisions.
Sujet(s)
Anémie/épidémiologie , Maladies du rein/épidémiologie , Tumeurs du foie/épidémiologie , Platine/usage thérapeutique , Tumeurs de la vessie urinaire/traitement médicamenteux , Urothélium/anatomopathologie , Sujet âgé , Sujet âgé de 80 ans ou plus , Évolution de la maladie , Europe/épidémiologie , Femelle , Humains , Tumeurs du foie/secondaire , Mâle , Métastase tumorale , Guides de bonnes pratiques cliniques comme sujet , Échec thérapeutique , Tumeurs de la vessie urinaire/complications , Tumeurs de la vessie urinaire/anatomopathologieRÉSUMÉ
Non-Muscle-Invasive-Bladder-Cancer represents 75-85% of the new bladder cancer cases per year. Trans-uretral vesical resection is the milestone for diagnosis and therapy. After primary treatment, recurrence is frequent depending on the presence of several established risk factors: multiplicity, T dimension, prior recurrence. In some patients disease progress to an advanced stage. Adjuvant chemo-immunotherapy has been widely used depending on the risk category assigned on the basis of the risk factors for recurrence. In low risk categories a one shot treatment with chemotherapy is considered the standard treatment without any maintenance therapy. In intermediate risk patients, adjuvant induction therapy and maintenance chemotherapy or immunotherapy for at least one year is recommended. In high risk patients adjuvant induction and maintenance immunotherapy until 3 years is considered the best strategy. In this review data on the different drugs used in this setting will be discussed.
Sujet(s)
Antinéoplasiques/usage thérapeutique , Immunothérapie/méthodes , Tumeurs de la vessie urinaire/thérapie , Antinéoplasiques/administration et posologie , Traitement médicamenteux adjuvant/méthodes , Association thérapeutique , Évolution de la maladie , Humains , Invasion tumorale , Récidive tumorale locale/prévention et contrôle , Stadification tumorale , Facteurs de risque , Facteurs temps , Tumeurs de la vessie urinaire/épidémiologie , Tumeurs de la vessie urinaire/anatomopathologieRÉSUMÉ
Endometrial cancer is a highly curable malignancy when it presents as uterine-confined disease, but the prognosis for metastatic or recurrent endometrial cancer is poor. For those patients which are diagnosed at an early stage, surgery alone may be adequate for cure and clinical outcome is often favorable, with approximately 80 % of cases surviving at 5 years. However, after primary diagnosis and treatment, roughly 20-30% of patients are expected to recur within the following 5 years. Adjuvant treatment for endometrial cancer is not yet clearly defined. FIGO Stage I-III endometrial cancer patients, usually undergo surgery and some of them are offered adjuvant treatment based on risk assessment. Grade, age, stage are considered all independent risk factors for recurrence. Radiotherapy (RT) has been considered the adjuvant treatment of choice for decades, being able to reduce local recurrence rate and improving progression free survival, but without any impact on overall survival. In the last two decades, a shift toward the use of systemic chemotherapy (CT) in addition or instead of radiation has occurred, although few prospective studies have been performed in this field.
Sujet(s)
Chimioradiothérapie adjuvante/méthodes , Tumeurs de l'endomètre/anatomopathologie , Tumeurs de l'endomètre/thérapie , Endomètre/anatomopathologie , Animaux , Antinéoplasiques/usage thérapeutique , Tumeurs de l'endomètre/épidémiologie , Tumeurs de l'endomètre/chirurgie , Endomètre/effets des médicaments et des substances chimiques , Endomètre/effets des radiations , Endomètre/chirurgie , Femelle , HumainsRÉSUMÉ
BACKGROUND: The aim of this study was to determine the maximum tolerated dose (MTD) of liposomal doxorubicin (LD)-vinorelbine (V) in patients with refractory or resistant ovarian cancer. PATIENTS AND METHODS: Thirty patients were eligible. Seven levels were studied [LD 25-V20 (three patients enrolled); LD 30-V20 (three); LD 35-V20 (three); LD 20-V25 (three); LD 25-V25 (three); LD 30-V25 (10); LD 35-V25 (five)]. LD was given on day 1, while V was given on days 1 and 8 every 21 days. Cohorts of three patients were enrolled at each level, and another three patients were planned, if one dose-limiting toxicity (DLT) was registered. RESULTS: DLT was observed in four patients: two febrile neutropenia, one grade 4 thrombocytopenia and one grade 3 palmar-plantar erythrodysesthesia (PPE) at level 7 (LD 35-V25). Thus, liposomal doxorubicin 30 mg/m(2) plus vinorelbine 25 mg/m(2) was the MTD. The most frequent toxicity was neutropenia. Fifteen patients (50%) experienced grade 3 neutropenia and 10 (33.3%) grade 4 neutropenia. Non-hematological toxicity was mild. Mucositis and PPE were the most frequent toxicities, but in most cases were grade 1. Out of 29 assessable patients, six (20.7%; 95% confidence interval 10%-39%) experienced an objective response, with one complete response. CONCLUSIONS: In patients with refractory or resistant ovarian cancer, the recommended doses for the combination studied are liposomal doxorubicin 30 mg/m(2) (day 1) plus vinorelbine 25 mg/m(2) (day 1 and 8). Neutropenia is the most frequent toxicity, while non-hematological toxicity is mild. Substantial activity was recorded and a phase II study is justified.
Sujet(s)
Antibiotiques antinéoplasiques/administration et posologie , Protocoles de polychimiothérapie antinéoplasique/administration et posologie , Doxorubicine/administration et posologie , Cellules épithéliales/anatomopathologie , Tumeurs de l'ovaire/traitement médicamenteux , Vinblastine/analogues et dérivés , Vinblastine/administration et posologie , Adulte , Sujet âgé , Antibiotiques antinéoplasiques/effets indésirables , Antibiotiques antinéoplasiques/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Études de cohortes , Relation dose-effet des médicaments , Doxorubicine/effets indésirables , Doxorubicine/usage thérapeutique , Résistance aux médicaments antinéoplasiques , Femelle , Humains , Liposomes , Dose maximale tolérée , Adulte d'âge moyen , Vinblastine/effets indésirables , Vinblastine/usage thérapeutique , VinorelbineRÉSUMÉ
BACKGROUND: Carboplatin is a milestone drug against ovarian carcinoma; it is used both in front-line and second-line chemotherapy. Hypersensitivity reactions to carboplatin may occur during the treatment as salvage therapy. The purpose of this study was to describe the feasibility of the replacing of carboplatin with cisplatin in patients presenting with severe hypersensitivity reactions to carboplatin. PATIENTS AND METHODS: Ten consecutive patients with platinum-sensitive, recurrent ovarian carcinoma, presenting with moderate/severe hypersensitivity reactions to carboplatin were treated with cisplatin 60 mg/m2 from January 2000 to December 2002. Hypersensitivity reactions consisted of respiratory distress (chest tightness, wheezing, dyspnea), urticaria/erythema with tachycardia, facial swelling and hypotension. RESULTS: The total number of cisplatin cycles given was 44 (range 2-5). The treatment with cisplatin was generally well tolerated. No serious allergic reactions occurred. A mild allergic reaction was recorded (urticaria) in only one case, after one cycle of cisplatin, and the patient was not rechallenged because of progressive disease. No reductions of chemotherapy doses were needed. CONCLUSION: To date, platinum-based regimens remain the most effective treatment in recurrent platinum-sensitive ovarian cancer with a high rate of objective responses. Although our experience is limited, we suggest that, under anesthesiologic surveillance and providing immunologic blockade, the replacement of carboplatin salvage therapy with cisplatin can be considered a safe therapeutic strategy in patients who cannot continue carboplatin due to allergic reactions.
Sujet(s)
Antinéoplasiques/effets indésirables , Antinéoplasiques/usage thérapeutique , Carboplatine/effets indésirables , Cisplatine/usage thérapeutique , Hypersensibilité médicamenteuse/étiologie , Récidive tumorale locale/traitement médicamenteux , Tumeurs de l'ovaire/traitement médicamenteux , Sujet âgé , Carboplatine/usage thérapeutique , Cisplatine/effets indésirables , Femelle , Humains , Adulte d'âge moyen , Récidive tumorale locale/immunologie , Tumeurs de l'ovaire/immunologie , Thérapie de rattrapageRÉSUMÉ
Fifty eight consecutive untreated patients with locally advanced cervical carcinoma (LACC) received neoadjuvant chemotherapy (NACT) with cisplatin (CDDP) 80 mg/sqm (day 1) + vinorelbine (VRL) 25 mg/sqm (day 1 and 8). Three cycles of chemotherapy were planned every 21 days. Within 28 days from the completion of chemotherapy patients in complete or partial response were submitted to radical hysterectomy with pelvic lymphadenectomy. On 155 cycles, hematologic toxicity was mild (G3-4 neutropenia and anemia occurred in 16% and 5%, respectively). Forty-seven patients (81%) were submitted to radical surgery; eight (14%) patients were deemed ineligible for surgery because of poor response to treatment, two (3%) for anesthesia contraindications and one (2%) refused surgery. At pathologic examination 12 patients (25%) had a complete response, one (2%) in-situ carcinoma, six (13%) residual microinvasive disease, and 28 (60%) a partial response. None had extracervical disease. Eight patients (14%) had microscopic lymph node metastases. The number of cycles administered was significantly associated with a good pathologic response. Association of CDDP and VRL as NACT in LACC appears safe and effective. Low cost and modest toxicity would support the initiation of a multicenter randomized phase III trial to compare this association with cisplatin alone.
Sujet(s)
Adénocarcinome/traitement médicamenteux , Protocoles de polychimiothérapie antinéoplasique/administration et posologie , Carcinome épidermoïde/traitement médicamenteux , Cisplatine/administration et posologie , Hystérectomie/méthodes , Tumeurs du col de l'utérus/traitement médicamenteux , Vinblastine/analogues et dérivés , Adénocarcinome/anatomopathologie , Adulte , Sujet âgé , Femelle , Humains , Adulte d'âge moyen , Traitement néoadjuvant , Stadification tumorale , Pronostic , Études prospectives , Résultat thérapeutique , Vinblastine/administration et posologie , VinorelbineSujet(s)
Ponction-biopsie à l'aiguille/instrumentation , Carcinome hépatocellulaire/secondaire , Tumeurs du foie/anatomopathologie , Essaimage tumoral , Tumeurs cutanées/secondaire , Sujet âgé , Carcinome hépatocellulaire/anatomopathologie , Hépatite C chronique/anatomopathologie , Humains , Foie/anatomopathologie , Mâle , Peau/anatomopathologie , Tumeurs cutanées/anatomopathologie , TomodensitométrieRÉSUMÉ
5-Fluorouracil (5-FU), in association with leucovorin (LV), is the most used chemotherapy agent in the treatment of colorectal cancer. Response rate, as well as side-effect incidence, increases with the dose intensity of regimens that are used. The most common dose-limiting toxicity for 5-FU/LV modulation is diarrhea. To assess the modification of small intestinal function, we investigated the changes in intestinal permeability (IP) and intestinal absorption (IA) in 41 chemo-naive patients (21 men and 22 women; mean age, 61 +/- 9 years) with advanced colorectal cancer after treatment with the association of folinic acid and 5-FU. After chemotherapy administration, we found a marked increase in IP and a reduction in IA, measured as cellobiose-mannitol (CE-MA) ratio (p < 0.0001) and D-xylose absorption (p = 0.0001), respectively. Patients who experienced diarrhea have an increase in CE-MA ratio and a reduction in D-xylose absorption values, both statistically significant. Cellobiose-mannitol ratio and D-xylose absorption tests can be used for the assessment of toxic effect of 5-FU on mature intestinal epithelium and also for evaluating the role of cytoprotective agents.
Sujet(s)
Antimétabolites antinéoplasiques/pharmacologie , Tumeurs colorectales/traitement médicamenteux , Tumeurs colorectales/métabolisme , Fluorouracil/pharmacologie , Antimétabolites antinéoplasiques/usage thérapeutique , Tumeurs colorectales/anatomopathologie , Fluorouracil/usage thérapeutique , Humains , Absorption intestinale , Stadification tumorale , PerméabilitéRÉSUMÉ
BACKGROUND: 5-Fluorouracil (FU) in association with folinic acid (FA) is the most frequently used chemotherapeutic agent in colorectal cancer but it often causes diarrhoea. Animal and human studies suggest that glutamine stimulates intestinal mucosal growth. AIM: To determine if oral glutamine prevents changes in intestinal absorption (IA) and permeability (IP) induced by FU/FA. METHODS: Seventy chemotherapy naive patients with colorectal cancer were randomly assigned to oral glutamine (18 g/day) or placebo before the first cycle of FU (450 mg/m(2)) and FA (100 mg/m(2)) administered intravenously for five days. Treatment was continued for 15 days, starting five days before the beginning of chemotherapy. IA (D-xylose urinary excretion) and IP (cellobiose-mannitol test) were assessed at baseline and four and five days after the end of the first cycle of chemotherapy, respectively. Patients kept a daily record of diarrhoea, scored using the classification system of the National Cancer Institute (Bethesda, Maryland, USA). Duration of diarrhoea was recorded and the area under the curve (AUC) was calculated for each patient. RESULTS: Baseline patient characteristics and basal values of IP and IA tests were similar in the two arms. After one cycle of chemotherapy, the reduction in IA (D-xylose absorption) was more marked in the placebo arm (7.1% v 3. 8%; p=0.02); reduction of IP to mannitol was higher in the placebo arm (9.2% v 4.5%; p=0.02); and urinary recovery of cellobiose was not different between the study arms (p=0.60). Accordingly, the cellobiose-mannitol ratio increased more in the placebo arm (0.037 v 0.012; p=0.04). Average AUC of diarrhoea (1.9 v 4.5; p=0.09) and average number of loperamide tablets taken (0.4 v 2.6; p=0.002) were reduced in the glutamine arm. CONCLUSIONS: Glutamine reduces changes in IA and IP induced by FU and may have a protective effect on FU induced diarrhoea.
Sujet(s)
Antimétabolites antinéoplasiques/effets indésirables , Diarrhée/prévention et contrôle , Fluorouracil/effets indésirables , Glutamine/administration et posologie , Administration par voie orale , Adulte , Sujet âgé , Tumeurs du côlon/complications , Tumeurs du côlon/traitement médicamenteux , Diarrhée/induit chimiquement , Méthode en double aveugle , Femelle , Humains , Absorption intestinale/effets des médicaments et des substances chimiques , Mâle , Adulte d'âge moyen , Statistique non paramétriqueRÉSUMÉ
The aim of the current study was to compare Levovist-enhanced power Doppler (PD) imaging with contrast-enhanced spiral computed tomography (CT) in the evaluation of intratumoral vascularity of hepatocellular carcinomas at diagnosis and after percutaneous ethanol injection (PEI). Nineteen patients with hepatocellular carcinoma (HCC) underwent PD with and without Levovist and spiral CT at diagnosis and 1 month after PEI treatment. Compared to spiral CT at baseline evaluation, the PD showed intratumoral vascularity in 36.8% of the cases; this percentage reached 78.9% after Levovist enhancement. One month after PEI, only 5 out of 19 treated HCCs appeared as hypodense areas at CT and showed no contrast enhancement. Only 3 of the 14 patients with a positive spiral CT scan were positive at the PD performed without the Levovist administration (sensitivity, 21.4%). The use of contrast-enhanced ultrasonography led to detection of residual signal in six other HCCs treated by ethanol injection (sensitivity, 64.2%). We confirm that spiral CT is the most sensitive and accurate technique in evaluating the effect of ethanol injection in HCC. It correctly identifies most cases of treatment failure as enhanced areas within the lesion. The lower rate of detection of tumoral vascularity by Doppler sonography was significantly increased by Levovist. The evidence of residual vascularity within HCC at Levovist Doppler sonography allows the targeting of additional ethanol injections.
Sujet(s)
Carcinome hépatocellulaire/diagnostic , Carcinome hépatocellulaire/traitement médicamenteux , Produits de contraste , Éthanol/administration et posologie , Tumeurs du foie/diagnostic , Tumeurs du foie/traitement médicamenteux , Polyosides , Tomodensitométrie/méthodes , Échographie-doppler/méthodes , Sujet âgé , Carcinome hépatocellulaire/vascularisation , Femelle , Humains , Amélioration d'image , Injections sous-cutanées , Tumeurs du foie/vascularisation , Mâle , Adulte d'âge moyen , Sensibilité et spécificitéRÉSUMÉ
BACKGROUND: Cisplatin and paclitaxel are active in cervical cancer and both are able to potentiate the effects of radiotherapy. In this study we evaluated the maximum-tolerated dose (MTD) of paclitaxel in combination with a fixed dose of cisplatin when given weekly concurrently with pelvic radiotherapy to patients with carcinoma of the cervix uteri. PATIENTS AND METHODS: Eighteen patients with cervical cancer were enrolled in this study. Cisplatin (30 mg/m2) and paclitaxel (starting dose 40 mg/m2; 5 mg/m2 escalation per level) were given on day 1 of radiotherapy and then weekly for six times. Radiotherapy was given to the pelvis with a four-field box technique for five days each week. Patients received 65 Gy in 1.8 Gy fractions. Cohorts of three patients were enrolled at each level and three further patients were included if one or two dose-limiting severe adverse events (SAE) were recorded. SAE was defined as grade 3 or 4 nonhematologic toxicity, excluding nausea or vomiting and alopecia, grade 4 neutropenia or thrombocytopenia, and prolonged (> 1 week) neutropenia or thrombocytopenia. RESULTS: Four levels were studied (paclitaxel 40, 45, 50, 55 mg/m2) with three, five, four and six patients enrolled, respectively. The MTD of paclitaxel was found at 50 mg/m2/wk and cisplatin 30 mg/m2/wk. Diarrhea was the dose-limiting toxicity. Thirteen patients were evaluable for response: seven complete and five partial responses were obtained with an overall response rate of 92.3%. CONCLUSIONS: The MTD of paclitaxel is 50 mg/m2/wk when associated to cisplatin 30 mg/m2/wk and concurrent pelvic radiotherapy. Diarrhea is the dose limiting side effect. Preliminary data suggest that concurrent chemoradiotherapy with paclitaxel and cisplatin could be a very active treatment for patients with locally advanced carcinoma of the cervix.
Sujet(s)
Adénocarcinome/traitement médicamenteux , Adénocarcinome/radiothérapie , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Carcinome épidermoïde/traitement médicamenteux , Carcinome épidermoïde/radiothérapie , Tumeurs du col de l'utérus/traitement médicamenteux , Tumeurs du col de l'utérus/radiothérapie , Adénocarcinome/anatomopathologie , Adulte , Sujet âgé , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Carcinome épidermoïde/anatomopathologie , Cisplatine/administration et posologie , Association thérapeutique , Diarrhée/induit chimiquement , Relation dose-effet des médicaments , Calendrier d'administration des médicaments , Femelle , Humains , Adulte d'âge moyen , Paclitaxel/administration et posologie , Taxoïdes , Tumeurs du col de l'utérus/anatomopathologieRÉSUMÉ
Chemotherapy has been proposed for patients with hepatocellular carcinoma (HCC) associated with well-compensated cirrhosis who are unsuitable for locoregional treatments. Anthracyclines are the most active agents against HCC, although their toxicity is often unpredictable; thus, there is a need for new active drugs with a safe toxicity profile. The liposomal formulation of the anthracycline daunorubicin has low systemic toxicity and is taken up strongly by the liver. We started a phase I study with liposomal daunorubicin (starting dose 80 mg/m2 every 21 days) in patients with hepatocellular carcinoma and Child-Pugh stage A or B liver cirrhosis. At the starting dose, we recorded dose-limiting toxicities (1 hyperbilirubinemia, 1 prolonged prothrombin time, 1 persisting grade 3 neutropenia) in 3 out of 4 patients. Thus, according to protocol, we went down to the dose level of 60 mg/m2 but still 2 out of 3 patients had unacceptable toxicity (1 hypertransaminasemia, 1 hyperbilirubinemia with encephalopathia). Finally, we treated 4 more patients at the dose level of 40 mg/m2 and again we recorded liver toxicity in three of them. Overall haematological toxicity was mild and significant non-haematologic toxicities, other than hepatic, were not recorded. The toxicity profile observed warns against further assessment of liposomal daunorubicin in patients with hepatocellular carcinoma and liver cirrhosis.