Introduction Despite 50 years of development experience, fundamental questions remain unanswered. The world still lacks a comprehensive theoretical framework that adequately explains such phenomenon as the accelerating velocity of development exhibited by East Asian countries, the failure of Malthusian projections, the growing contribution of non-material resources not subject to depletion, the apparent failure of market policies in the transition of Eastern Europe, and conflicting predictions about the future of work based on the contrary recent experiences of North America and Western Europe. A profusion of economic theories provide explanations for specific expressions of development, but none unite the pieces into a unified theory that adequately defines the central principles, process and stages of development. The formulation of a comprehensive theory of development would make conscious the world's experience over the past years, reveal enormous untapped potentials and vastly accelerate the speed of future progress.
University of Southern California standing order for the management of hypersensitivity reactions. IVP, intravenous push; prn, as needed; q, every.
Most patients who experience a mild-to-moderate reaction grade 1 or 2 during the first exposure, such as those often seen with taxanes and monoclonal antibodies, will tolerate readministration of the agent using a slower infusion rate and premedication after all symptoms have resolved [ 161114202739 ].
Rechallenge is generally discouraged in patients who have a severe initial reaction grade 3 or 4underscoring the need for accurate grading of hypersensitivity reactions and infusion reactions Table 1.
Premedication for rechallenge typically includes antihistamines and corticosteroids [ 6 ]. For monoclonal antibodies, reducing the infusion rate by half e. Desensitization protocols have been used with some success in patients who experience severe hypersensitivity reactions to taxanes [ 91139 ].
Mild-to-moderate reactions to platinum compounds generally do not require treatment discontinuation [ 7 ]. Many patients can continue therapy or be rechallenged after symptoms have resolved using pretreatment with antihistamines and corticosteroids [ 45723 ].
However, rechallenge with platinum compounds is generally less successful than with taxanes: Similar to taxanes, desensitization protocols modifying infusion times have been used with success to reduce the risk of a second reaction to platinum agents [ 24840 ].
Some of these protocols are based on reinstating treatment at a low concentration and progressively increasing the concentration of the drug by administering a sequence of serial dilutions i.
This approach has been successful in rechallenging patients who had experienced reactions to carboplatin and oxaliplatin.
As those patients undergo safe infusions after a reaction, premedications can be used for subsequent doses [ 41 ].
In any circumstance, the decision to rechallenge with any agent should be based on several clinical factors, including the risk for a serious recurrent reaction and the potential clinical benefit of further treatment.
For example, if the drug is given as salvage therapy or as palliative care, the long-term clinical benefits of continued treatment are likely to be small and may not warrant the risk for severe toxicity. In this case, switching to an alternative agent, if available, may be appropriate.
However, continuing active treatment should be a priority for patients who have mild-to-moderate reactions, and strategies that safely allow continuation should be considered, particularly if the goal of therapy is to prolong survival.
The decision to continue or discontinue treatment must be made on a case-by-case basis after weighing all of the relevant clinical factors. Accurate grading of hypersensitivity and infusion reactions, including distinguishing between moderate and more severe reactions, may be critical to determine the best treatment plan following resolution of symptoms.
Previous Section Next Section Conclusions Although severe reactions are rare, mild-to-moderate hypersensitivity or infusion reactions occur frequently with many commonly used systemic cancer therapies, including platinum compounds, taxanes, and monoclonal antibodies.
The clinical symptoms of these reactions are remarkably similar, regardless of the type of agent or proposed mechanism. One important difference among these agents is the time of onset of symptoms. Hypersensitivity to platinum compounds typically develops after multiple cycles of therapy, suggesting that it is an acquired, anaphylactic reaction consistent with type 1 hypersensitivity.
In contrast, reactions to taxanes and monoclonal antibodies are immediate, often occurring within the first few minutes of the first infusion, which suggests that these reactions occur by alternative mechanisms. The risk for severe hypersensitivity reactions can possibly be reduced by checking for a history of drug allergies, adequate premedication, careful patient monitoring, and prompt intervention when signs of hypersensitivity occur.
Accurate grading of reactions is essential in determining how to proceed with treatment. Mild-to-moderate reactions are managed by temporarily interrupting the infusion and administering supportive care for symptoms.
For severe reactions, the infusion should be stopped, supportive care should be provided, and, in most cases, treatment should be discontinued.Peer Commentary.
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