The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
David S. Alberts - One of the best experts on this subject based on the ideXlab platform.
-
Pretreatment CA-125 and Risk of Relapse in Advanced Ovarian Cancer
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2006Co-Authors: Maurie Markman, P. Y. Liu, Mace L. Rothenberg, Bradley J. Monk, Mark Brady, David S. AlbertsAbstract:Purpose A previous report suggested the nadir serum CA-125 level within the group of patients with ovarian cancer who achieved normalization of CA-125 accurately defined the risk of relapse. Using similar CA-125 subgroups, we sought to determine if the baseline CA-125 level before initiation of maintenance chemotherapy in women achieving a clinically-defined complete response to primary chemotherapy would be of prognostic value. Patients and Methods Patients included in this retrospective analysis had been treated on one of two previously reported trials of maintenance chemotherapy (three v 12-monthly cycles of paclitaxel; oral Altretamine), with a baseline CA-125 level of ≤ 35 u/mL. Progression-free survival (PFS) from study entry was analyzed by the Cox regression model. Results The distribution of premaintenance baseline CA-125 levels for the 384 patients was 58%, 34%, and 8% for values of (A) ≤ 10 u/mL, (B) 11 to 20 u/mL, and (C) 21 to 35 u/mL, respectively. The baseline CA-125 was highly statisticall...
-
Relationship between pretreatment CA-125 level and risk of relapse in advanced ovarian cancer (AOC) patients in a complete clinical response (CCR) who received “maintenance therapy”
Journal of Clinical Oncology, 2005Co-Authors: P. Y. Liu, David S. Alberts, Bradley J. Monk, M. F. Brady, Maurie MarkmanAbstract:5013 Background: Patients (pts) with AOC who achieve a CCR have a high risk of recurrence. Reliable methods to identify the risk of relapse may lead to modifications in disease management. Methods: Crawford, et al. (Proc ASCO 2004: 23:448) showed that AOC pts with a nadir CA-125 level of ≤ 10 experienced substantially improved 2-year progression-free survival (PFS), compared to pts whose CA-125 ranged from 11–20 or 21–30. Using these criteria but with entry CA-125, we analyzed the risk of progression in pts treated on 2 trials of “maintenance therapy” (MT) in women with AOC who attained a CCR following primary chemotherapy (CT): (1) phase 2 SWOG trial of Altretamine (260 mg/m2 daily x 14 days, repeated monthly x 6 months (m)) (n=97); (2) phase 3 SWOG/GOG trial of paclitaxel (175 mg/m2 over 3 hours for 3 or 12 m) (n=287). Pts must enter the trials no later than 8 weeks after the last dose of prior CT. Pretreatment CA-125 was ≤ 35 for all pts. PFS from study entry was analyzed by the Cox regression model st...
-
Long-term follow-up of a phase II trial of oral Altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 2004Co-Authors: David S. Alberts, Maurie Markman, C. Jiang, P. Y. Liu, Sharon P. Wilczynski, Mace L. RothenbergAbstract:Objective This report provides follow-up progression-free survival (PFS) and median survival data for women who achieved clinical complete remission (cCR) from stage III ovarian cancer after first-line therapy and were treated with Altretamine consolidation therapy. Methods Patients who enrolled in the SWOG 9326 study from September 1993 to July 1997 were required to have documented cCR from stage III ovarian cancer following front-line platinum-based therapy. Treatment consisted of 6 months of oral Altretamine at 260 mg/m2/day for 14 consecutive days of a 28-day cycle. Results Ninety-seven of 112 enrolled patients were evaluable for efficacy. This report presents median 6.2-year follow-up, dating from study registration. Median PFS was 28 (95% CI: 19–43) months. Median PFS for patients with optimal disease was 45 (95% CI: 27–48) months and for patients with suboptimal disease was 17 (95% CI: 12–26) months. Twenty-six of 61 (43%) patients with optimally debulked lesions and 5 of 36 (14%) patients with suboptimally debulked lesions remained disease free. Median survival of patients with optimally debulked disease has not been reached; median survival of patients with suboptimally debulked disease was 39 (95% CI: 19–51) months. No treatment-related adverse events were reported during the follow-up period. Conclusions Consolidation therapy with oral Altretamine was generally well tolerated and associated with prolonged progression-free and overall survival in the Phase II setting.
-
Treatment of refractory and recurrent ovarian cancer
Seminars in Oncology, 1999Co-Authors: David S. AlbertsAbstract:Patients with recurrent ovarian cancer can be divided into two groups: those who have recurrence more than 6 months after primary therapy with paclitaxel/platinum (ie, platinum-sensitive) and those with tumor progression or recurrence within 6 months of primary therapy (ie, platinum-resistant). In patients with platinum-sensitive tumors and good performance status, re-treatment with paclitaxel/platinum combination therapy is usually the most appropriate choice. For patients with minimum residual disease, the greatest promise for long-term disease-free survival is associated with intensive intraperitoneal therapy with combinations of cisplatin and intravenous/intraperitoneal paclitaxel. Alternatively, patients with platinum-sensitive disease can receive intravenous carboplatin or paclitaxel. Patients with platinum-resistant ovarian cancer can benefit from single-agent therapy with Altretamine, topotecan, oral etoposide, ifosfamide, liposomal doxorubicin, or other standard or investigational regimens. (Of these drugs, only Altretamine and topotecan are approved by the US Food and Drug Administration for persistent or recurrent ovarian cancer.) Since the response rates achieved with these drugs are similar, patient convenience, side effects, and cost may play a significant role in drug selection.
Pharnuk Suthipinijtham - One of the best experts on this subject based on the ideXlab platform.
-
Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with Altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model
Cancer Chemotherapy and Pharmacology, 2008Co-Authors: Michael J Kelner, Leita A. Estes, Rafael J. Rojas, Trevor C Mcmorris, Pharnuk SuthipinijthamAbstract:Purpose Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O’Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)^2 system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway. Methods The human lung carcinoma MV522 cell line and its corresponding xenograft model were used to evaluate the activity of irofulven in combination with different DNA damaging agents. Results Two main classes of DNA damaging agents, platinum-derived agents, and select bifunctional alkylating agents, demonstrated in vivo synergistic or super-additive interaction with irofulven. DNA helicase inhibiting agents also demonstrated synergy in vitro, but an enhanced interaction with irofulven could not be demonstrated in vivo. There was no detectable synergistic activity between irofulven and agents capable of inducing DNA cleavage or intercalating into DNA. Conclusion These results indicate that the antitumor activity of irofulven is enhanced when combined with platinum-derived agents, Altretamine, and select alkylating agents such as melphalan or chlorambucil. A common factor between these agents appears to be the production of intrastrand DNA crosslinks. The synergistic interaction between irofulven and other agents may stem from the nucleotide excision repair system being selectively overwhelmed at two distinct points in the pathway, resulting in prolonged stalling of transcription forks, and subsequent initiation of apoptosis.
-
Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with Altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model
Cancer Chemotherapy and Pharmacology, 2008Co-Authors: Michael J Kelner, Leita A. Estes, Trevor C Mcmorris, Rafael Rojas, Pharnuk SuthipinijthamAbstract:Purpose Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O’Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)2 system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway.
Maurie Markman - One of the best experts on this subject based on the ideXlab platform.
-
Pretreatment CA-125 and Risk of Relapse in Advanced Ovarian Cancer
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2006Co-Authors: Maurie Markman, P. Y. Liu, Mace L. Rothenberg, Bradley J. Monk, Mark Brady, David S. AlbertsAbstract:Purpose A previous report suggested the nadir serum CA-125 level within the group of patients with ovarian cancer who achieved normalization of CA-125 accurately defined the risk of relapse. Using similar CA-125 subgroups, we sought to determine if the baseline CA-125 level before initiation of maintenance chemotherapy in women achieving a clinically-defined complete response to primary chemotherapy would be of prognostic value. Patients and Methods Patients included in this retrospective analysis had been treated on one of two previously reported trials of maintenance chemotherapy (three v 12-monthly cycles of paclitaxel; oral Altretamine), with a baseline CA-125 level of ≤ 35 u/mL. Progression-free survival (PFS) from study entry was analyzed by the Cox regression model. Results The distribution of premaintenance baseline CA-125 levels for the 384 patients was 58%, 34%, and 8% for values of (A) ≤ 10 u/mL, (B) 11 to 20 u/mL, and (C) 21 to 35 u/mL, respectively. The baseline CA-125 was highly statisticall...
-
Relationship between pretreatment CA-125 level and risk of relapse in advanced ovarian cancer (AOC) patients in a complete clinical response (CCR) who received “maintenance therapy”
Journal of Clinical Oncology, 2005Co-Authors: P. Y. Liu, David S. Alberts, Bradley J. Monk, M. F. Brady, Maurie MarkmanAbstract:5013 Background: Patients (pts) with AOC who achieve a CCR have a high risk of recurrence. Reliable methods to identify the risk of relapse may lead to modifications in disease management. Methods: Crawford, et al. (Proc ASCO 2004: 23:448) showed that AOC pts with a nadir CA-125 level of ≤ 10 experienced substantially improved 2-year progression-free survival (PFS), compared to pts whose CA-125 ranged from 11–20 or 21–30. Using these criteria but with entry CA-125, we analyzed the risk of progression in pts treated on 2 trials of “maintenance therapy” (MT) in women with AOC who attained a CCR following primary chemotherapy (CT): (1) phase 2 SWOG trial of Altretamine (260 mg/m2 daily x 14 days, repeated monthly x 6 months (m)) (n=97); (2) phase 3 SWOG/GOG trial of paclitaxel (175 mg/m2 over 3 hours for 3 or 12 m) (n=287). Pts must enter the trials no later than 8 weeks after the last dose of prior CT. Pretreatment CA-125 was ≤ 35 for all pts. PFS from study entry was analyzed by the Cox regression model st...
-
Long-term follow-up of a phase II trial of oral Altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 2004Co-Authors: David S. Alberts, Maurie Markman, C. Jiang, P. Y. Liu, Sharon P. Wilczynski, Mace L. RothenbergAbstract:Objective This report provides follow-up progression-free survival (PFS) and median survival data for women who achieved clinical complete remission (cCR) from stage III ovarian cancer after first-line therapy and were treated with Altretamine consolidation therapy. Methods Patients who enrolled in the SWOG 9326 study from September 1993 to July 1997 were required to have documented cCR from stage III ovarian cancer following front-line platinum-based therapy. Treatment consisted of 6 months of oral Altretamine at 260 mg/m2/day for 14 consecutive days of a 28-day cycle. Results Ninety-seven of 112 enrolled patients were evaluable for efficacy. This report presents median 6.2-year follow-up, dating from study registration. Median PFS was 28 (95% CI: 19–43) months. Median PFS for patients with optimal disease was 45 (95% CI: 27–48) months and for patients with suboptimal disease was 17 (95% CI: 12–26) months. Twenty-six of 61 (43%) patients with optimally debulked lesions and 5 of 36 (14%) patients with suboptimally debulked lesions remained disease free. Median survival of patients with optimally debulked disease has not been reached; median survival of patients with suboptimally debulked disease was 39 (95% CI: 19–51) months. No treatment-related adverse events were reported during the follow-up period. Conclusions Consolidation therapy with oral Altretamine was generally well tolerated and associated with prolonged progression-free and overall survival in the Phase II setting.
-
Altretamine (Hexamethylmelamine) in Platinum-Resistant and Platinum-Refractory Ovarian Cancer: A Gynecologic Oncology Group Phase II Trial
Gynecologic oncology, 1998Co-Authors: Maurie Markman, John A. Blessing, David H. Moore, Harrison Ball, Samuel S. LentzAbstract:Abstract Objectives. In an effort to critically examine the antitumor activity of Altretamine (hexamethylmelamine) as salvage therapy of platinum-refractory ovarian cancer, the Gynecologic Oncology Group initiated a Phase II trial of the agent administered in this clinical setting. Methods. Altretamine was administered at a dose of 260 mg/m 2 orally for 14 days in a 28-day course. Treatment was continued until disease progression or unacceptable side effects prevented further therapy. A total of 36 patients (median age: 56.5) were treated on this trial, of whom 33 were evaluable for toxicity and 30 for response. All patients had previously received either cisplatin or carboplatin and paclitaxel. Results. The major side effect was emesis (grade 3–4,733, 21%). The objective response rate was 10% (one complete response, two partial responses). Conclusion. We conclude that Altretamine has limited activity in platinum-refractory ovarian cancer.
Amber Vyas - One of the best experts on this subject based on the ideXlab platform.
-
pharmacokinetic study of solid lipid nanoparticles of Altretamine complexed epichlorohydrin β cyclodextrin for enhanced solubility and oral bioavailability
International Journal of Biological Macromolecules, 2017Co-Authors: Bina Gidwani, Amber VyasAbstract:Altretamine is a synthetic drug approved for treatment of ovarian cancer. The only drawback with its formulation is poor aqueous solubility and low oral bioavailability. In the present work an attempt has been made to prepare inclusion complex of Altretamine with epichlorohydrin beta cyclodextrin. The complexes were prepared by kneading, co-evaporation and freeze-drying method and were confirmed by FTIR, XRD, DSC, drug content and dissolution study. Kneaded complex possess maximum solubilizing efficiency of 82.63 in 25mM Epi-β-CD solution. SLNs of pure Altretamine and ALT complexed with Epi-β-CD were prepared by modified emulsification-ultrasonication method. The particle size and zeta potential was found to be 151.5nm and -21.3mV. The drug release pattern of SLNs was bi-phasic in nature; with an initial burst release followed by sustained drug release. Pharmacokinetic study showed that the average Cmax was found to be 0.94μg/ml, which was 2.47 times higher as compared to the pure drug. The AUCt for SLNs was 150minμgh/ml and 54minμgh/ml for pure ALT suspension which proved that the SLNs exhibited greater absorption compared to the pure drug. Thus, smaller particle size, higher entrapment efficiency and enhanced aqueous solubility led to improvement in oral bioavailability of ALT.
-
Designing and evaluation of extended release matrix tablet containing Altretamine–HP-β-CD inclusion complex
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2015Co-Authors: Bina Gidwani, Amber VyasAbstract:The aim of present study was to prepare sustained release tablets of a poorly soluble anticancer drug using cyclodextrin complexation as a potential approach. Altretamine is an alkylating agent practically insoluble in water and posses poor oral bioavailability. For this, the most suitable binary system of ALT-HP-β-CD was selected to improve the aqueous solubility and then embedding the complexed drug into a matrix tablet with fusion method. Tablets were prepared using glycerol monostearate (GMS) and polyethylene glycol 4000 (PEG4000). Complexes were prepared at different ratios and mixed with other excipients to achieve tablets with efficient dissolution profile complying with the requirements for sustained delivery of solid dosage forms. Results of Fourier Infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) proved that kneading was most efficient technique for preparation of amorphous cyclodextrin inclusion complex with ALT and entrapping this complex into tablet. Dissolution profile of ALT was enhanced significantly in pH 6.8 from the binary system and significant within the limits ( t test Student p
-
Designing and evaluation of extended release matrix tablet containing Altretamine–HP-β-CD inclusion complex
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2015Co-Authors: Bina Gidwani, Amber VyasAbstract:The aim of present study was to prepare sustained release tablets of a poorly soluble anticancer drug using cyclodextrin complexation as a potential approach. Altretamine is an alkylating agent practically insoluble in water and posses poor oral bioavailability. For this, the most suitable binary system of ALT-HP-β-CD was selected to improve the aqueous solubility and then embedding the complexed drug into a matrix tablet with fusion method. Tablets were prepared using glycerol monostearate (GMS) and polyethylene glycol 4000 (PEG4000). Complexes were prepared at different ratios and mixed with other excipients to achieve tablets with efficient dissolution profile complying with the requirements for sustained delivery of solid dosage forms. Results of Fourier Infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) proved that kneading was most efficient technique for preparation of amorphous cyclodextrin inclusion complex with ALT and entrapping this complex into tablet. Dissolution profile of ALT was enhanced significantly in pH 6.8 from the binary system and significant within the limits (t test Student p < 0.05). The release kinetics of the tablets showed that diffusion was responsible for controlling the release from the tablets.
-
Preparation, characterization, and optimization of Altretamine-loaded solid lipid nanoparticles using Box-Behnken design and response surface methodology.
Artificial cells nanomedicine and biotechnology, 2014Co-Authors: Bina Gidwani, Amber VyasAbstract:The objective of the present study was to prepare solid lipid nanoparticles (SLNs) of Altretamine (ALT) by the hot homogenization and ultrasonication method. The study was conducted using the Box-Behnken design (BBD), with a 33 design and a total of 17 experimental runs, performed in combination with response surface methodology (RSM). The SLNs were evaluated for mean particle size, entrapment efficiency, and drug-loading. The optimized formulation, with a desirability factor of 0.92, was selected and characterized. In vitro release studies showed a biphasic release pattern from the SLNs for up to 24 h. The results of % EE (93.21 ± 1.5), %DL (1.15 ± 0.6), and mean diameter of (100.6 ± 2.1) nm, were very close to the predicted values.
Peter C. Kohler - One of the best experts on this subject based on the ideXlab platform.
-
Phase II trial of oral Altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer: a Southwest Oncology Group trial (SWOG-9326).
Gynecologic oncology, 2001Co-Authors: Mace L. Rothenberg, Sharon P. Wilczynski, Poching Liu, Edward V. Hannigan, S. Weiner, Geoffrey R. Weiss, Verda J. Hunter, Julia A. Chapman, Amy Tiersten, Peter C. KohlerAbstract:Abstract Objective. The aim of this study was to evaluate the 2-year survival rate in a group of women in complete clinical remission (cCR) from Stage III ovarian cancer following front-line therapy who were then treated with a 6-month course of Altretamine. Methods. Patients were documented to be in cCR by physical examination, computed tomography or magnetic resonance imaging scan, and serum CA-125. Treatment consisted of Altretamine (Hexalen)® 260 mg/m 2 /day po divided into four doses taken after meals and at bedtime for 14 of 28 days for six cycles. Based on previous experience in the Southwest Oncology Group, the treatment would be considered promising if the 2-year survival rate was ≥65% as measured from study registration. Results. From 9/1/93 and 7/1/97, 112 patients were registered and 97 were fully evaluable. The majority of patients had optimally debulked (≤1 cm: 63%), high-grade (Grade 3: 82%) tumors. The 2-year survival rate in this study was 75% (95% CI: 66–84%). For those patients with optimal disease, the 2-year survival rate was 82% (95% CI: 72–92%) and for those with suboptimal disease it was 64% (95% CI: 48–79%). Four patients (4%) experienced Grade 4 and 21 patients (22%) experienced Grade 3 toxicities consisting primarily of nausea/vomiting, neutropenia, fatigue, anxiety, and paresthesias. Conclusions. The 2-year survival rate in this study warrants further evaluation of consolidation therapy for women in clinical complete remission following front-line chemotherapy for Stage III ovarian cancer. Caution is advised in the interpretation of these data, however, because of the nonrandomized nature of the trial and the unknown contribution of front-line use of paclitaxel to the durability of clinical complete response.
