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  • Writer's pictureDr. Robert A. Nagourney, MD

Challenging Paradigms: The Management of Rectal Cancer

Summary


At the recent American Society of Clinical Oncology meeting, a shift in treatment focus from 'Maximum Tolerated' to 'Minimum Effective' was highlighted. This trend prioritizes optimal dosage over high dosage, ensuring less toxicity and better outcomes. This approach is particularly evident in rectal cancer treatment, where non-surgical methods are now more popular. One noteworthy case was a 78-year-old patient successfully treated without surgery due to careful dose adjustments, underscoring the value of personalized treatment strategies.


Full Article


The recent American Society of Clinical Oncology (ASCO) meeting held in Chicago in June had several interesting areas of focus. One prominent theme was the need to reduce doses and the intensity of therapy to maintain good outcomes with less toxicity.


Whether in childhood cancer where late toxicities can be life threatening, or breast cancer where radiation is being limited, or drug dosing where less is now more, the focus has clearly clocked around from Maximum Tolerated (yesteryears’ approach) to Minimum Effective (today’s breakthrough).


Our laboratory platform long ago allowed us to recognize that drugs work because they are the right drug, not because you “Dose-to-the Max”.


This trend is perhaps most evident in the management of rectal cancer where a movement, originally spearheaded by Angelita Habr-Gama of Sao Paolo Brazil, to apply non-surgical management to locally advanced rectal cancers has taken off. This approach often saves patients this disfiguring procedure.


We have applied this approach in many patients and have succeeded in avoiding surgery or reduced the need for colostomy. One case is particularly gratifying.


A Delay in Diagnosis


This 78-year-old gentleman had a delay in diagnosis of several months. By the time we met, his large, low-lying cancer seemed a likely candidate for colostomy, but he was adamantly opposed.


I explained the concept promoted by Dr. Habr-Gama, whereby pre-operative therapy could be followed with close observation saving him possible surgery. This has now been widely adopted by American oncologists using what is known as Total-Neoadjuvant-Treatment, or TNT.


The question remained; could a 78-year-old gentleman with cardiac disease, diabetes, hypertension and a host of other conditions, get through the rigorous schedule of chemotherapies and radiation?


We began treatment. The toxicity, mostly from the radiation side effects, proved challenging. Getting him through it with the help of my staff, it was then that the final piece of the puzzle needed to be assembled.


A single cycle of low dose FOLFOXIRI literally knocked his socks off, despite significant dose reduction. But we needed to finish the job. Without effective treatment, he was heading for colostomy. When I suggested using chemotherapy to avoid surgery, his gastroenterologist was scandalized.


But here was a golden opportunity to apply what we had learned from our many years of laboratory experience and the insights into drug action, drug interaction, mode of action and synergy in human cancer that we had published over the years.


I am reminded of the famous quote from the Battle of Ben Tre during the Vietnam war that took place on February 7, 1968. The commanding officer explained the need for intensive bombing and shelling and was quoted, “We had to destroy the village to save it”.


I had absolutely no intention of destroying my patent to save him, so cooler heads needed to prevail.


Cooler Heads Prevail


Having published comparative studies between Topotecan and Irinotecan (Nagourney RA: Br J Cancer 2003), we know we could substitute the better tolerated Topotecan for the more toxic Irinotecan in the FOLFOXIRI regimen and save him GI toxicity.


Having previously compared Cisplatin to Oxaliplatin in human tissue (Evans, SS Proc ASCO May 2000), we knew we could substitute Cisplatin for Oxaliplatin and save the patient from neurotoxicity.


Finally, our seminal work in the development of Capecitabine under contract with Roche and published experience with this drug alone and in combination (Brewer, Proc AACR, 2007) allowed us to craft an oral alternative to the more toxic IV 5-FU infusions.


We applied our chemotherapeutic wizardry to great effect and with almost no toxicity.


Now after two years, it has worked beautifully. The MRIs are clear, and the follow up colonoscopy biopsies are negative. He is back to a normal life.


Every patient deserves the treatment that is right for them.


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