Volasertib and Platinum Agent Combination for Solid Tumours
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Solution Overview
Problem
Current treatments for advanced and/or metastatic solid tumours often result in tumour progression and death, highlighting the need for new therapeutic strategies that combine chemotherapeutic agents with different modes of action and improved dosage schedules.
Innovation Solution
The combination of Volasertib, a potent inhibitor of Polo like kinase 1, with Cisplatin or Carboplatin, administered in specific dosage schedules, including varying daily doses and body surface area-based dosing, to treat advanced and/or metastatic solid tumours, with options ranging from 300 to 500 mg of Volasertib and 50 to 100 mg/m2 of Cisplatin or targeted AUC doses of Carboplatin, across different treatment cycles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard chemotherapeutic treatments are used, then tumour shrinkage may be achieved, but tumour progression and death occur due to lack of durable response
Solution Approach 1:
The patent combines two chemotherapeutic agents with different mechanisms of action: Volasertib (a Plk1 inhibitor that disrupts cell cycle progression) and Cisplatin/Carboplatin (platinum-based DNA crosslinking agents). This combination therapy aims to achieve synergistic anti-tumour effects and improve durable response rates compared to monotherapy, directly addressing the lack of sustained therapeutic benefit in standard treatments
2Reliability
If combination therapy with multiple chemotherapeutic agents is administered, then therapeutic efficacy is improved, but side effects and toxicity increase
Solution Approach 1:
The patent employs dynamic dosage adjustment based on body surface area (BSA) and treatment cycle progression. Volasertib is administered at 300-500 mg on day 1 of each 21-day cycle, while Cisplatin/Carboplatin dosages are adjusted according to BSA and renal function. This dynamic dosing strategy optimizes therapeutic efficacy while managing toxicity, allowing patients to receive effective combination therapy without overwhelming side effects
3Reliability
If high dosages of chemotherapeutic agents are administered, then tumour response is improved, but myelosuppression and other severe side effects are potentiated
Solution Approach 1:
The patent utilizes parameter changes in dosing schedules, administering Volasertib at 300-500 mg (preferred 350 mg) and Cisplatin/Carboplatin at specific BSA-based dosages on day 1 of 21-day cycles. This structured parameter adjustment ensures high enough dosages to achieve tumour response while distributing the therapeutic load over time to prevent severe myelosuppression. The patent also includes dose modification guidelines based on observed toxicity levels
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This combination therapy demonstrates partial responses and stable disease in patients with various solid tumours, indicating improved therapeutic efficacy with manageable side effects, as shown in clinical trials.
Implementation Method 1
Volasertib is a highly potent and selective inhibitor of the serine-threonine Polo like kinase 1 (Plk1), a key regulator of cell-cycle progression
Implementation Method 2
It reacts in vivo, binding to and causing crosslinking of DNA, which ultimately triggers apoptosis
Implementation Method 3
Carboplatin interact with DNA, similar to the mechanism of alkylating agents
Data Source
AI summary
The present invention relates to the use of Volasertib or a salt thereof or a hydrate thereof in combination with Cisplatin or Carboplatin or a salt thereof or a hydrate thereof for treating patients suffering from advanced and/or metastatic solid tumors.