Pixantrone

Key takeaways

Pixantrone belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Pixantrone to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Pixantrone from memory before moving on to harder problems.

Reference excerpt

Pixantrone (rINN; trade name Pixuvri) is an experimental antineoplastic (anti-cancer) drug, an analogue of mitoxantrone with fewer toxic effects on cardiac tissue. It acts as a topoisomerase II poison and intercalating agent. The code name BBR 2778 refers to pixantrone dimaleate, the actual substance commonly used in clinical trials.

History Anthracyclines are important chemotherapy agents. However, their use is associated with irreversible and cumulative heart damage. Investigators have attempted to design related drugs that maintain the biological activity, but do not possess the cardiotoxicity of the anthracyclines. Pixantrone was developed to reduce heart damage related to treatment while retaining efficacy. Random screening at the US National Cancer Institute of a vast number of compounds provided by the Allied Chemical Company led to the discovery of ametantrone as having significant anti-tumor activity. Further investigation regarding the rational development of analogs of ametantrone led to the synthesis of mitoxantrone, which also exhibited marked anti-tumor activity Mitoxantrone was considered as an analog of doxorubicin with less structural complexity but with a similar mode of action. In clinical studies, mitoxantrone was shown to be effective against numerous types of tumors with less toxic side effects than those resulting from doxorubicin therapy. However, mitoxantrone was not totally free of cardiotoxicity. A number of structurally modified analogs of mitoxantrone were synthesized and structure-activity relationship studies made. BBR 2778 was originally synthesized by University of Vermont researchers Miles P. Hacker and Paul A. Krapcho and initially characterized in vitro for tumor cell cytotoxicity and mechanism of action by studies at the Boehringer Mannheim Italia Research Center, Monza, and University of Vermont, Burlington. Other studies have been completed at the University of Texas M. D. Anderson Cancer Center, Houston, the Istituto Nazionale Tumori, Milan, and the University of Padua. In the search for novel heteroanalogs of anthracenediones, it was selected as the most promising compound. Toxicological studies indicated that BBR 2778 was not cardiotoxic, and US patents are held by the University of Vermont. An additional US patent application was completed in June 1995 by Boehringer Mannheim, Italy. Novuspharma, an Italian company, was established in 1998 following the merger of Boehringer Mannheim and Hoffmann-La Roche, and BBR 2778 was developed as Novuspharma's leading anti-cancer drug, pixantrone. A patent application for the injectable preparation was filed in May 2003. In 2003, Cell Therapeutics, a Seattle biotechnology company, acquired pixantrone through a merger with Novuspharma.

Clinical trials Pixantrone is a substance that is being studied in the treatment of cancer. It belongs to the family of drugs called antitumor antibiotics. phase III clinical trials of pixantrone have been completed. Pixantrone is being studied as an antineoplastic for different kinds of cancer, including solid tumors and hematological malignancies such as non-Hodgkin lymphomas. Animal studies demonstrated that pixantrone does not worsen pre-existing heart muscle damage, suggesting that pixantrone may be useful in patients pretreated with anthracyclines. While only minimal cardiac changes are observed in mice given repeated cycles of pixantrone, 2 cycles of traditional anthracyclines doxorubicin or mitoxantrone result in marked or severe heart muscle degeneration. Clinical trials substituting pixantrone for doxorubicin in standard first-line treatment of patients with aggressive non-Hodgkin's lymphoma, had a reduction in severe side effects when compared to patients treated with standard doxorubicin-based therapy. Despite pixantrone patients receiving more treatment cycles, a three-fold reduction in the incidence of severe heart damage was seen as well as clinically significant reductions in infections and thrombocytopenia, and a significant reduction in febrile neutropenia. These findings could have major implications for treating patients with breast cancer, lymphoma, and leukemia, where debilitating cardiac damage from doxorubicin might be prevented. Previous treatment options for multiply relapsed aggressive non-Hodgkin lymphoma had disappointing response rates. The completed phase II RAPID trial compared the CHOP-R regimen of Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, and Rituximab to the same regimen, but substituting Doxorubicin with Pixantrone. The objective was to show that Pixantrone was not inferior to Doxorubicin and less toxic to the heart. Pixantrone was shown to have potentially reduced cardiotoxicity and demonstrated promising clinical activity in these phase II studies in heavily pretreated non-Hodgkin lymphoma patients. The phase III EXTEND (PIX301) randomized clinical trial studied pixantrone to see how well it works compared to other chemotherapy drugs in treating participants with relapsed non-Hodgkin's lymphoma. The complete response rate in pixantrone treated with pixantrone has been significantly higher than in those receiving other chemotherapeutic agents for treatment of relapsed/refractory aggressive non-Hodgkin lymphoma.

Administration It can be administered through a peripheral vein rather than a central implanted catheter as required for other similar drugs.

Society and culture

Legal status

US Food and Drug Administration The US Food and Drug Administration (FDA) granted fast track designation for pixantrone in people who had previously been treated two or more times for relapsed or refractory aggressive Non-Hodgkin's Lymphoma. Study sponsor Cell Therapeutics announced that pixantrone achieved the primary efficacy endpoint. The minutes of the Oncologic Drugs Advisory Committee meeting of 22 March 2010 show that this had not in fact been achieved with statistical significance and this combined with major safety concerns lead to the conclusion that the trial was not sufficient to support approval. In April 2010, the FDA asked for an additional trial.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Pixantrone

Start with the simplest possible case. Write down what Pixantrone claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Pixantrone before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Pixantrone ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Pixantrone

In research: Pixantrone appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Pixantrone in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Pixantrone is common in secondary-school and first-year university syllabi. It links to neighbouring topics Aminoethyl compounds, DNA intercalaters, Enones, so understanding it makes those chapters shorter.
In everyday life: Look for Pixantrone outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Pixantrone in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Pixantrone means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Pixantrone out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Pixantrone in simple terms?

Pixantrone (rINN; trade name Pixuvri) is an experimental antineoplastic (anti-cancer) drug, an analogue of mitoxantrone with fewer toxic effects on cardiac tissue. It acts as a topoisomerase II poison and intercalating agent.

Why does Pixantrone matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Pixantrone?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Pixantrone.