共查询到20条相似文献,搜索用时 15 毫秒
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Axel Le Cesne Jean-Yves Blay Binh Nguyen Bui Olivier Bouché Antoine Adenis Julien Domont Angela Cioffi Isabelle Ray-Coquard Nathalie Lassau Sylvie Bonvalot Alain Moussy Jean-Pierre Kinet Olivier Hermine 《European journal of cancer (Oxford, England : 1990)》2010,46(8):1344-1351
BackgroundMasitinib is a tyrosine kinase inhibitor with greater in vitro activity and selectivity for the wild-type c-Kit receptor and its juxtamembrane mutation than imatinib, without inhibiting kinases of known toxicities. This phase II study evaluated masitinib as a first-line treatment of advanced GIST.Patients and methodsImatinib-naïve patients with advanced GIST received oral masitinib at 7.5 mg/kg/d. Efficacy end-points included response rate (RR) at 2 months, best response according to RECIST, metabolic response rate, disease control rate (DCR), progression-free survival (PFS) and overall survival rate (OS).ResultsThirty patients were enrolled with a median follow-up of 34 months. The most frequent grade 3–4 toxicities were rash (10%) and neutropaenia (7%). Two patients withdrew due to treatment-related adverse events. At 2 months, RR was 20% according to response evaluation criteria in solid tumours (RECIST) and 86% according to FDG-PET response criteria. Best responses were a complete response in 1/30 patient (3.3%), partial response in 15/30 patients (50%), stable disease in 13/30 patients (43.3%) and progressive disease in 1/30 patient (3.3%); (DCR: 96.7%). Median time-to-response was 5.6 months (0.8–23.8 months). Estimated median PFS was 41.3 months with PFS rate of 59.7% [37.9; 76.0] and 55.4 [33.9; 72.5] at 2 and 3 years, respectively. The OS at 2 and 3 years was stable at 89.9% [71.8; 96.6].ConclusionsMasitinib appears to be effective as a first-line treatment of advanced GIST with comparable results to imatinib in terms of safety and response. PFS and in particular OS data show promise that masitinib may provide sustainable benefits. There is sufficient compelling evidence to warrant a phase III clinical trial. 相似文献
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Markus Moehler Rolf Mahlberg Volker Heinemann Radka Obermannová Eugen Kubala Bohuslav Melichar Arndt Weinmann Paul Scigalla Marietta Tesařová Petr Janda Fabienne Hédouin-Biville Wasat Mansoor 《Gastric cancer》2017,20(2):358-367
Background
This phase I study investigated the safety and the maximum tolerated dose (MTD) of the oral fluoropyrimidine S-1 when combined with epirubicin and oxaliplatin (EOS).Methods
Patients aged ≥18 years with advanced or metastatic solid tumors were enrolled in a 3 + 3 design with S-1 dose escalation (two planned cohorts) performed according to the occurrence of dose-limiting toxicity (DLT). On day 1 of each 21-day cycle, patients received epirubicin 50 mg/m2 followed by oxaliplatin 130 mg/m2 (maximum 8 cycles) and then S-1 [20 mg/m2 (cohort 1) or 25 mg/m2 (cohort 2), twice daily]: first dose, evening of day 1; subsequent administration on days 2–14, twice daily; last dose, morning of day 15 (unlimited number of S-1 cycles). After protocol amendment, enrollment in a third cohort was restricted to patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer.Results
DLT was reported for two of the five patients in cohort 2, defining 20 mg/m2 twice daily as the MTD of S-1 combined with epirubicin and oxaliplatin in heavily pretreated patients. Thirteen patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer were subsequently enrolled and treated at an S-1 dose level of 25 mg/m2 twice daily; no DLTs were reported; median overall survival was 13.1 months. Of the 11 evaluable patients, three (27 %) had partial responses and seven (64 %) had stable disease. The safety profile was in line with expectations.Conclusions
The promising activity of EOS (S-1 dose level, 25 mg/m2 twice daily) and acceptable safety profile support further clinical development of this combination for the first-line treatment of patients with advanced or metastatic esophagogastric cancer.7.
William R. Schelman Sherry Morgan-Meadows Rebecca Marnocha Fred Lee Jens Eickhoff Wei Huang Marcia Pomplun Zhisheng Jiang Dona Alberti Jill M. Kolesar Percy Ivy George Wilding Anne M. Traynor 《Cancer chemotherapy and pharmacology》2009,63(6):1147-1156
Purpose
To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine® administered in combination with doxorubicin.Study design
Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine® IV on days 1–4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m2 and Triapine® 25 mg/m2. PK analysis was performed at various time-points before and after treatment.Results
Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m2, Triapine® 45 mg/m2), two patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional three patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m2) with Triapine® 45 mg/m2. The two patients enrolled on this level had two DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine® were reduced to 45 and 25 mg/m2, respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer.Conclusions
Pretreated patients with advanced malignancies can tolerate the combination of Triapine® and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m2 on day 1 and Triapine® 25 mg/m2 on days 1–4 of a 21-day cycle. 相似文献8.
Johann S de Bono Nicole Concin David S Hong Fiona C Thistlethwaite Jean-Pascal Machiels Hendrik-Tobias Arkenau Ruth Plummer Robert Hugh Jones Dorte Nielsen Kristian Windfeld Srinivas Ghatta Brian M Slomovitz James F Spicer Jeffrey Yachnin Joo Ern Ang Paul Morten Mau-Sørensen Martin David Forster Dearbhaile Collins Ulrik Lassen 《The lancet oncology》2019,20(3):383-393
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Gyeong-Won Lee Hye Jung Kim Ji-Hyun Ju Seok-Hyun Kim Hoon Gu Kim Tae Hyo Kim Hyun Jin Kim Chi-Young Jeong Jung Hun Kang 《Cancer chemotherapy and pharmacology》2009,64(4):707-713
Background
We performed a phase II study of combination chemotherapy with S-1 plus gemcitabine for treating chemo-naïve patients with unresectable pancreatic cancer to evaluate the efficacy and toxicity.Patients and methods
Patients with histologically confirmed unresectable pancreatic cancer were eligible. The treatment consisted of S-1 (40 mg/m2 p.o. b.i.d. from D1 to 14) and gemcitabine (1,250 mg/m2 on D1 and 8), repeated every 3 weeks.Results
Thirty-two patients were enrolled between March 2005 and December 2007. No complete response was observed and a partial response was observed in 14 patients (44.0%), stable disease in eight patients (25.0%), and progressive disease in eight patients (25.0%). The median time to progression was 4.92 months (95% CI: 4.16–5.67 months), and the median overall survival was 7.89 months (95% CI: 5.96–9.82 months). The survival duration was significantly longer for the patients with a good performance status compared with that of the patients with a poor performance status. The major toxicities were grade 3–4 neutropenia (9, 28.1%), grade 3/4 thrombocytopenia (5, 15.6%), and grade 3 diarrhea (5, 15.6%).Conclusion
The combination chemotherapy of S-1 and gemcitabine showed promising antitumor activity and manageable toxicities, and especially for the good performance status patients with unresectable pancreatic cancer. 相似文献10.
Kyriakos P. Papadopoulos Howard A. Burris III Michael Gordon Peter Lee Edward A. Sausville Peter J. Rosen Amita Patnaik Richard E. Cutler Jr. Zhengping Wang Susan Lee Suzanne F. Jones Jeffery R. Infante 《Cancer chemotherapy and pharmacology》2013,72(4):861-868
Purpose
Tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of carfilzomib, a selective proteasome inhibitor, administered twice weekly by 2–10-min intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 in 28-day cycles, were assessed in patients with advanced solid tumors in this phase I/II study.Methods
Adult patients with solid tumors progressing after ≥1 prior therapies were enrolled. The dose was 20 mg/m2 in week 1 of cycle 1 and 20, 27, or 36 mg/m2 thereafter. The maximum tolerated dose or protocol-defined maximum planned dose (MPD) identified during dose escalation was administered to an expansion cohort and to patients with small cell lung, non-small cell lung, ovarian, and renal cancer in phase II tumor-specific cohorts.Results
Fourteen patients received carfilzomib during dose escalation. The single dose-limiting toxicity at 20/36 mg/m2 was grade 3 fatigue, establishing the MPD as the expansion and phase II dose. Sixty-five additional patients received carfilzomib at the MPD. Adverse events included fatigue, nausea, anorexia, and dyspnea. Carfilzomib PK was dose proportional with a half-life <1 h. All doses resulted in at least 80 % proteasome inhibition in blood. Partial responses occurred in two patients in phase I, with 21.5 % stable disease after four cycles in evaluable patients in the expansion and phase II cohorts.Conclusion
Carfilzomib 20/36 mg/m2 was well tolerated when administered twice weekly by 2–10-min IV infusion. At this dose and infusion rate, carfilzomib inhibited the proteasome in blood but demonstrated limited antitumor activity in patients with advanced solid tumors. 相似文献11.
Ignacio Garrido-Laguna Ian Krop Howard A. Burris III Erika Hamilton Fadi Braiteh Amy M. Weise Maysa Abu-Khalaf Theresa L. Werner Steven Pirie-Shepherd Christopher J. Zopf Mani Lakshminarayanan Jaymes S. Holland Raffaele Baffa David S. Hong 《International journal of cancer. Journal international du cancer》2019,145(7):1798-1808
PF-06647263, a novel antibody–drug conjugate consisting of an anti-EFNA4 antibody linked to a calicheamicin payload, has shown potent antitumor activity in human xenograft tumor models, including triple-negative breast cancer (TNBC). In the dose-escalation part 1 of this multicenter, open-label, phase I study (NCT02078752), successive cohorts of patients (n, 48) with advanced solid tumors and no available standard therapy received PF-06647263 every 3 weeks (Q3W) or every week (QW), following a modified toxicity probability interval (mTPI) method (initial dosing: 0.015 mg/kg Q3W). Primary objective in part 1 was to estimate the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D). In part 2 (dose-expansion cohort), 12 patients with pretreated, metastatic TNBC received PF-06647263 at the RP2D to further evaluate tumor response and overall safety. PF-06647263 QW administration (n, 23) was better tolerated than the Q3W regimen (n, 25) with only 1 DLT reported (thrombocytopenia). The most common AEs with the QW regimen (fatigue, nausea, vomiting, mucosal inflammation, thrombocytopenia, and diarrhea) were mostly mild to moderate in severity. The MTD was not estimated. PF-06647263 exposures increased in a dose-related manner across the doses evaluated. The RP2D was determined to be 0.015 mg/kg QW. Six (10%) patients achieved a confirmed partial response and 22 (36.7%) patients had stable disease. No correlations were observed between tumor responses and EFNA4 expression levels. Study findings showed manageable safety and favorable PK for PF-06647263 administered QW at the RP2D, with preliminary evidence of limited antitumor activity in patients with TNBC and ovarian cancer. 相似文献
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《Annals of oncology》2010,21(2):382-388
BackgroundThe aim of this study was to determine the maximum tolerated dose (MTD) and the pharmacokinetic profile of Genexol-PM in Asian cancer patients.Materials and methodsPatients (N = 24) refractory to previous chemotherapy received Genexol-PM as an 1-h infusion on a weekly basis for 3 weeks followed by a resting week. The starting dose was 80 mg/m2 and the maximum administered dose was 200 mg/m2.ResultsThe majority of patients had lung, nasopharyngeal and breast cancers and in eleven patients (46%), taxane-based chemotherapy had previously failed. The MTD was defined at 180 mg/m2. The most common grade 3 non-hematologic adverse events in cycle 1 were fatigue (4%) and neuropathy (4%) occurring mainly at 200 mg/m2. Five (21%) patients had partial response, nine (38%) had stable disease and seven (29%) had disease progression. Five of 11 previously taxane-refractory patients showed clinical benefit to Genexol-PM. The pharmacokinetics of Genexol-PM displayed dose-proportionality, with both the maximum concentration (Cmax) and the area under the concentration-time curve from zero to infinity (AUC0–∞) increasing by approximately four- and threefold, respectively, as the dose of Genexol-PM was escalated from 80 to 200 mg/m2. The median total-body clearance of Genexol-PM for all patients was 43.9 l/h.ConclusionThe weekly regimen of Genexol-PM was well tolerated and responses were observed in patients with refractory tumors, including patients who had failed taxane-based chemotherapy previously. 相似文献
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Phase I and pharmacokinetic study of anhydrovinblastine every 3 weeks in patients with refractory solid tumors 总被引:1,自引:0,他引:1
Ramnath N Schwartz GN Smith P Bong D Kanter P Berdzik J Creaven PJ 《Cancer chemotherapy and pharmacology》2003,51(3):227-230
PURPOSE: Anhydrovinblastine (AVLB) is a novel semisynthetic vinca alkaloid. We conducted a phase I trial to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT) and pharmacokinetics of AVLB given as a 1-h intravenous infusion once every 3 weeks in patients with advanced refractory solid tumors. PATIENTS AND METHODS: Entered into the study were 24 patients with normal bone marrow, hepatic and renal function, and of these 21 were evaluable. There were 12 males and 12 females with a median age of 60 years (range 27-75 years). Diagnoses were non-small-cell lung cancer (NSCLC) (11), colorectal cancer (5), soft tissue sarcoma (4), and miscellaneous (4). Patients had had a median of three prior chemotherapy regimens (range one to six). A total of 51 courses were administered at doses of 2.5, 5, 10, 16.5, 21, 25 and 30 mg/m(2) in one, three, one, three, six, six and one patient respectively. RESULTS: Grade 2 infusional hypertension, anemia, and dizziness were noted at 16.5 mg/m(2). At 25 mg/m(2), two of six evaluable patients had DLT. DLT was grade 4 constipation, neutropenia and grade 3 nausea/vomiting. At 21 mg/m(2) one of six evaluable patients had DLT (grade 3 nausea/vomiting). This dose was the MTD. Stable disease was noted in one patient with metastatic sarcoma to the lungs and in three patients with metastatic NSCLC. The pharmacokinetics of AVLB were linear, and well characterized by a two-compartment model, with a mean clearance of 26.4 l/h per m(2) and median terminal half-life of 18 h. CONCLUSIONS: The recommended phase II dose is 21 mg/m(2). A phase II study in NSCLC is being initiated. 相似文献
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DuBois SG Shusterman S Reid JM Ingle AM Ahern CH Baruchel S Glade-Bender J Ivy P Adamson PC Blaney SM 《Cancer chemotherapy and pharmacology》2012,69(4):1021-1027
Purpose
Sunitinib is an oral tyrosine kinase inhibitor of VEGF, PDGF, c-KIT, and flt-3 receptors. A pediatric phase I study of sunitinib capsules identified the maximum tolerated dose as 15 mg/m2/day. This study was conducted to evaluate sunitinib given as a powder formulation. 相似文献15.
High incidence of central nervous system involvement in patients with?metastatic or locally advanced breast cancer treated with epirubicin?and?docetaxel 总被引:11,自引:4,他引:7
D. Crivellari O. Pagani A. Veronesi D. Lombardi F. Nolè B. Thürlimann D. Hess M. Borner J. Bauer G Martinelli R. Graffeo C. Sessa A. Goldhirsch 《Annals of oncology》2001,12(3):353-356
Background:Clinically overt central nervous system (CNS)involvement occurs in 10%–15% of patients with advancedbreast cancer.
Patients and methods:The International Breast Cancer Study Group(IBCSG) conducted a dose-finding phase I trial of epirubicin (E) and docetaxel(D) as first-line therapy in advanced breast cancer patients. The study wasexpanded into a phase II at the recommended doses of E 90 mg/m2 andD 75 mg/m2 every three weeks. From July 1996 to May 1998, a totalof 92 patients (median age 50 years) entered the two studies.
Results:Twenty-eight out of ninety-two patients treated with thecombination of E and D (30%) developed CNS metastases (95%confidence limits, 26%-35%), which were cerebral in twenty-fivepatients, leptomeningeal in two, and both in one. Of these 28 patients, 19(68%) had an objective response. Median time for the development of CNSmetastases from the start of chemotherapy was 15 months (range 5–42),if excluding the 6 patients presenting CNS progression within 3 months fromstart of treatment. It is notable that 11 patients (39%) hadprogression in the CNS only. Median survival from appearance of brainmetastases in the whole group was only three months (range 1–22).C-erbB-2 overexpression was found in 14 out of 16 patients (87%) inwhom the assay was performed (3+ in 10, 2+ in 1 and 1+ in 3 cases).
Conclusions:As anthracycline- and taxane-containing regimens areincreasingly used both in the metastatic and in the adjuvant setting, acareful monitoring of any neurological symptom is advisable. Our preliminaryobservation on the possible increase of incidence of CNS involvement inpatients with advanced breast cancer receiving this effective drug combinationrequires further evaluation. 相似文献
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Pitot HC Adjei AA Reid JM Sloan JA Atherton PJ Rubin J Alberts SR Duncan BA Denis L Schaaf LJ Yin D Sharma A McGovren P Miller LL Erlichman C 《Cancer chemotherapy and pharmacology》2006,58(2):165-172
Purpose: Intravenous (i.v.) irinotecan is a cytotoxic topoisomerase I inhibitor with broad clinical activity in metastatic colorectal cancer and other tumors. The development of an oral formulation of irinotecan could enhance convenience and lessen the expense of palliative irinotecan delivery. This phase I study evaluated the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of irinotecan given as a powder-filled capsule (PFC) daily for 5 days every 3 weeks. Patients and methods: Patients with advanced solid tumors received escalating doses of oral irinotecan daily for 5 days every 3 weeks. Plasma samples were collected following the first and fifth doses of irinotecan during Cycle 1 to determine the PK of irinotecan and its major circulating metabolites: SN-38, SN-38G, and APC. Results: 20 patients (median age 61.5 years, range 40–75; M/F 12/8; ECOG PS 0=5, 1=11, 2=4) received oral irinotecan at dose levels of 30 (n=3), 40 (n=3), 50 (n=6), and 60 (n=8) mg/m2/day. Of the eight patients enrolled at 60 mg/m2, three patients experienced DLT (≥ grade 3) consisting of nausea (three patients), vomiting (three patients), diarrhea (two patients), and febrile neutropenia (two patients) for which all the three patients required hospitalization. Treatment of six patients at the 50-mg/m2 dose level resulted in no DLT. Other toxicities observed include abdominal pain, alopecia, anorexia, and asthenia. After oral administration, irinotecan was rapidly absorbed into systemic circulation and converted to the active metabolite SN-38. Increasing dose levels resulted in a dose-dependent increase in mean exposure parameters (Cmax and AUC) of irinotecan and metabolites. Systemic exposure parameters (Cmax and AUC0-24) of irinotecan and SN-38 were comparable between days 1 and 5. The extent of conversion from irinotecan to SN-38 was approximately threefold higher after the oral administration compared to that previously observed after i.v. administration. The exposure parameters of irinotecan or SN-38 are of limited value in predicting severity of Cycle 1 toxicities in the twofold dose range evaluated. Conclusion: Daily oral administration of irinotecan as the PFC formulation for 5 days every 3 weeks can safely deliver protracted exposure to SN-38, with the MTD of 50 mg/m2/d.Supported in part by Pharmacia and National Cancer Institute Grants U01-CA69912, M01-RR00585, and CA15083-26 相似文献
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《Annals of oncology》2010,21(11):2278-2283
PurposeRECIST have limitations when applied to potentially curable locally advanced squamous cell carcinoma of the head and neck (SCCHN). [18F]fluorodeoxyglucose–positron emission tomography (PET) scan may be useful in assessing treatment response and predicting patient outcome.Patients and methodsWe studied patients with previously untreated stages III–IVb SCCHN treated with primary concurrent chemoradiotherapy on five prospective clinical trials. Response was assessed by clinical exam, computed tomography (CT), and PET portions of combined PET–CT scan ∼8 weeks after completion of chemoradiotherapy.ResultsFifty-three patients were analyzed. Complete response (CR) was demonstrated in 42 patients (79%) by clinical exam, 15 (28%) by CT, and 27 (51%) by PET. CR as assessed by PET, but not as assessed by clinical exam or CT using RECIST, correlated significantly with progression-free status (PFS) (P < 0.0001). The 2-year PFS for patients with CR and without CR by PET was 93% and 48%, respectively (P = 0.0002).ConclusionsA negative PET scan on combined PET–CT after chemoradiotherapy is a powerful predictor of outcome in patients receiving curative chemoradiotherapy for SCCHN. PET–CT is indicated for response evaluation in this setting to improve the accuracy of post-treatment assessment by CT. 相似文献
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J. Capdevila S. Clive E. Casado C. Michie A. Piera E. Sicart M. J. Carreras C. Coronado C. Kahatt A. Soto Matos-Pita C. Fernandez Teruel M. Siguero M. Cullell-Young J. Tabernero 《Cancer chemotherapy and pharmacology》2013,71(5):1247-1254
Purpose
PM00104 (Zalypsis®) is a synthetic tetrahydroisoquinoline alkaloid with potent antiproliferative activity against tumor cell lines. This phase I study evaluated the safety, dose-limiting toxicities (DLTs), recommended dose for phase II trials (RD), pharmacokinetics (PK) and preliminary antitumor activity of PM00104 as a 24-h intravenous (i.v.) infusion every 3 weeks (q3wk).Methods
Thirty-seven patients with refractory advanced solid tumors received PM00104 in a toxicity-guided dose escalation study design (3 + 3 patients per cohort). Plasma samples were collected for PK analysis.Results
DLTs comprised severe neutropenia lasting >5 days (n = 4 patients), vomiting, thrombocytopenia, transaminase increases (n = 2 each), fatigue, tumor pain, myalgia, muscle stiffness, creatine phosphokinase increase and dosing delay >2 weeks due to moderate fatigue (n = 1 each). The RD was 4.0 mg/m2. Most PM00104-related adverse events at the RD were mild or moderate; the most common were nausea, vomiting and fatigue. Myelosuppression and transaminase increases were transient and manageable. PK parameters increased linearly with dose. Higher PM00104 PK exposure was related to a decrease in hemoglobin, neutrophils, platelets and white blood cells. Area under the curve was directly correlated with both incidence and severity of nausea and vomiting. Three patients with hepatocellular carcinoma, esophageal adenocarcinoma and prostate adenocarcinoma had response evaluation criteria in solid tumors stable disease ≥3 months.Conclusions
PM00104 given as 24-h i.v. infusion q3wk has predictable and manageable toxicity, but resulted in more myelotoxicity (because of the higher dose level achieved as the RD) and a similar drug clearance compared to 1-h infusion schedules. Preliminary evidence of antitumor activity was observed. 相似文献19.
The treatment of metastatic melanoma is still undergoing a process of major change. The two most important novel therapeutic strategies, selective kinase inhibitors and immune checkpoint blockers, both significantly prolong survival times of patients with advanced metastatic disease. Different agents, dose regimens and combinations have been tested against each other vigorously within these two groups. However, results from prospective head-to-head comparative studies of both strategies are still lacking. We performed an exploratory analysis of survival data from selected clinical trials representative for the new treatment strategies in advanced metastatic melanoma. Eighty-three Kaplan–Meier survival curves from 25 trials were digitised and grouped by therapeutic strategy and treatment line. For each of these groups, mean survival curves were generated for progression-free (PFS) and overall survival (OS) by weighted averaging. Survival curves grouped together by therapeutic strategy revealed a high concordance, particularly in the first-line setting. For kinase inhibitors, the most favourable PFS and OS in all therapy lines were observed for combined BRAF plus MEK inhibition. For immune checkpoint inhibitors, combined PD-1 plus CTLA-4 inhibition demonstrated the best survival outcome in all categories except for OS in first-line therapy. For the latter, combined PD-1 plus CTLA-4 inhibition showed similar outcomes as single-agent PD-1 inhibition. Comparison of kinase inhibitors and checkpoint blockers revealed a superiority of combined BRAF plus MEK inhibition within the first 6 months, later changing to a superiority of PD-1 blockers alone or in combination with CTLA-4 blockers. These results need confirmation by prospective clinical trials. 相似文献