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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, 2006
    Co-Authors: Maurie Markman, Mace L. Rothenberg, P. Y. Liu, Bradley J. Monk, Mark Brady, David S. Alberts

    Abstract:

    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, 2005
    Co-Authors: P. Y. Liu, David S. Alberts, Bradley J. Monk, M. F. Brady, Maurie Markman

    Abstract:

    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, 2004
    Co-Authors: David S. Alberts, Maurie Markman, C. Jiang, P. Y. Liu, Sharon P. Wilczynski, Mace L. Rothenberg

    Abstract:

    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.

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, 2008
    Co-Authors: Michael J Kelner, Trevor C Mcmorris, Leita A. Estes, Rafael J. Rojas, Pharnuk Suthipinijtham

    Abstract:

    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, 2008
    Co-Authors: Michael J Kelner, Trevor C Mcmorris, Rafael Rojas, Leita A. Estes, Pharnuk Suthipinijtham

    Abstract:

    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, 2006
    Co-Authors: Maurie Markman, Mace L. Rothenberg, P. Y. Liu, Bradley J. Monk, Mark Brady, David S. Alberts

    Abstract:

    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, 2005
    Co-Authors: P. Y. Liu, David S. Alberts, Bradley J. Monk, M. F. Brady, Maurie Markman

    Abstract:

    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, 2004
    Co-Authors: David S. Alberts, Maurie Markman, C. Jiang, P. Y. Liu, Sharon P. Wilczynski, Mace L. Rothenberg

    Abstract:

    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.