As recently as 2004, standard first line treatment for kids with neuroblastoma consisted of seven cycles of chemotherapy. As some of you may recall from my prior posts, chemotherapy is by no means a smart bomb; that is, in addition to targeting neuroblastoma cells, chemo also damages healthy cells throughout the body. It is for this reason that now whenever he watches T.V. or listens to music, Toby has to crank up the volume and ask (always politely) those around him to speak quietly. This is also the reason why Toby painfully struggles with horrible constipation; why he has headaches, lightheadedness, and a resting heart rate that most of us reach only with vigorous exercise; why he easily bleeds and bruises, often with no preceding trauma or other obvious trigger; and why routine coughs and colds most of us don't give much thought to are so potentially dangerous for Toby. These are the immediate consequences of chemotherapy. They are serious, frustrating, and life-altering. However, they pale in comparison to the possible long-term side effects like, infertility, deafness, heart and kidney failure, nerve damage, hormonal imbalance, secondary cancer, and even death. The last two are particularly ironic. Because of these significant "toxicities," doctors and scientists are continually trying to come up with more effective and less toxic treatments. In the case of neuroblastoma, such an approach was achieved by reducing the number of initial rounds of chemo from seven to five and by adding things like antibody treatment. Unfortunately, five cycles of chemo is not enough to rid all kids of their neuroblastoma. In these cases the first option often means resorting to a sixth or even seventh cycle of more chemo - this is what Toby has to look forward to.
After five cycles of chemo, Toby still had evidence of neuroblastoma in various parts of his body so he had a sixth cycle, incorporating one drug he had yet to be exposed to. Following the sixth cycle and radiation to his arm, Toby had re-evaluation scans; as you know from Mooki's most recent post, the news is not good. Toby still has disease in his bone marrow, as well as in his femur (the long bone in the leg). What this means is that Toby's disease is classified as primary refractory disease. What is the reason for the refractoriness? I'm not sure there's a single answer, but one answer Toby's doctor suggested relates to the significant amount of disease that Toby had when he was initially diagnosed, which is taking extra cycles to clear. I believe that the actual biology of the neuroblastoma is at play here as well. Whatever the reasons, Toby is now scheduled for a seventh round of chemo to start this Monday. This time he will be given three drugs he has never received, with the idea that the neuroblastoma cells might be (more) susceptible to this cocktail. Because most kids with neuroblastoma do not require more than five cycles, there is not much evidence as to the efficacy of these three agents, carboplatin/temozolomide/irinotecan. However, the toxicities of these drugs is known.
Carboplatin is a cousin of cisplatin, a drug which Toby received during cycles 3 and 5 and which can lead to an assortment of side effects including, hearing loss, kidney damage, altered nerve sensation, and low blood counts. Temozolomide also causes low blood counts, as well as nausea, vomiting, bruising (because it drops the platelet count), tingling in the hands and feet, and insomnia. Finally, there is irinotecan, best known for the severe diarrhea it causes. In addition, it can cause low blood counts, hair loss (so much for Toby's regenerating follicles) headache, sweating, and mouth sores.
Mooki and Stephen are anxiously awaiting the next phase of treatment which follows chemo - 3F8 antibody treatment. 3F8 acts in a different way than chemo. Chemo destroys cells, often by targeting a part of the cell responsible for cell replication or by preventing cells from correcting parts of the cell that are damaged. 3F8 on the other hand, is a biologic drug, it works in a different way by targeting certain cell receptors found only on neuroblastoma cells. For 3F8 to work most effectively neuroblastoma has to be completely or almost completely eradicated. This is the reason for an "unlucky" seventh cycle of chemo.
Mooki and Stephen desperately want to move on to 3F8 and its potential for making things right. They have mixed feelings about more chemo and are especially wary of the likely side effects, but like so many times until now they signed the consent forms agreeing to move on in the hope that this cycle will allow them to reach that goal.
Hoping is hard. I hope that my job as a pediatric hematologist/oncologist doesn't get in the way of the more important job of being Toby's uncle and Mooki's brother. I hope that I can think like a humanist and not like a doctor. I hope that Toby won't need hearing aides and I hope for hope.
Ed Clark, Christmas Guest
4 months ago