Intermittent GRM Dosing with Taxane Chemotherapy
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Solution Overview
Problem
Current treatments for ovarian, fallopian tube, uterine, cervical, vaginal, vulvar, and peritoneal cancers, particularly platinum-resistant cases, are limited in effectiveness and tolerability, leading to poor outcomes for patients.
Innovation Solution
The use of intermittent administration of glucocorticoid receptor modulator (GRM) compounds, such as nonsteroidal GRMs like relacorilant, in combination with cancer chemotherapy, specifically taxane chemotherapy, to enhance treatment efficacy and reduce side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If continuous chemotherapy is administered to treat platinum-resistant ovarian cancer, then cancer cell proliferation is reduced and tumor-cell apoptosis is promoted, but treatment efficacy diminishes over time and recurrence rate increases
Solution Approach 1:
The patent employs intermittent dosing of glucocorticoid receptor modulators (GRMs) combined with chemotherapy cycles, where treatment is administered periodically rather than continuously. This approach involves giving GRMs on specific days (e.g., days 1-3 or 1-5 of a 21 or 28-day cycle) followed by drug-free intervals, allowing the body to recover while maintaining anti-cancer efficacy through repeated cycles.
Solution Approach 2:
The patent introduces dynamic treatment protocols that adapt the dosing schedule of GRMs based on treatment response and patient tolerance. The regimen can be adjusted between cycles, modifying the intensity and frequency of GRM administration to optimize therapeutic effect while managing toxicity, thereby extending progression-free survival.
2Productivity
If high-dose chemotherapy is administered to maximize cancer cell destruction, then tumor-cell apoptosis is increased, but side effects and toxicity increase
Solution Approach 1:
The patent uses glucocorticoid receptor modulators as intermediary agents that enhance the anti-cancer effect of chemotherapy while potentially reducing its toxicity. GRMs act as mediators that modulate the immune system and inflammatory responses, amplifying the therapeutic benefit of chemotherapy while protecting normal tissues from excessive damage.
Solution Approach 2:
The patent modifies treatment parameters by introducing intermittent dosing schedules with varying GRM doses and frequencies. By changing the dosing parameters (dose amount, frequency, and duration) rather than maintaining constant high-dose chemotherapy, the treatment achieves effective cancer cell destruction while allowing recovery periods that reduce cumulative toxicity.
3Reliability
If standard chemotherapy regimens are used for recurrent ovarian cancer, then some patients achieve response, but the duration of response is short and overall survival remains limited
Solution Approach 1:
The patent combines glucocorticoid receptor modulators with standard chemotherapy regimens in an integrated treatment approach. This combination therapy merges the direct cytotoxic effect of chemotherapy with the immunomodulatory and anti-inflammatory effects of GRMs, creating a synergistic treatment that extends the duration of response beyond what either agent achieves alone.
Solution Approach 2:
The patent implements continuous treatment strategies through repeated cycles of intermittent GRM dosing combined with chemotherapy. Rather than single-course treatment, the regimen maintains continuous therapeutic pressure on the cancer through multiple cycles, each building on the previous response, thereby extending the overall duration of response and progression-free survival.
Data Source
AI summary
Methods and compositions for treating cancer (e.g., ovarian, fallopian tube, uterine, cervical, vaginal, vulvar, or peritoneal cancer) are disclosed. The methods include intermittent administration of a glucocorticoid receptor modulator (GRM), such as a non-steroidal GRM (e.g., relacorilant), which may be orally administered, along with a cancer chemotherapy agent (such as, e.g., bevacizumab) to the patient. The GRM may be administered: at intervals separated by at least one day without GRM administration; by a schedule linked to the cancer chemotherapy schedule (e.g., a weekly chemotherapy regimen); the day of, or the day before, or the day after, chemotherapy administration; by combinations thereof; and/or on other days. Ovarian cancer patients receiving intermittent relacorilant administration along with nab-paclitaxel administration had improved overall survival, improved progression free survival, improved duration of response, and other benefits as compared to patients not receiving relacorilant while receiving nab-paclitaxel.