This Summer came and went so quickly – back to school for the kids in a few days. The last few months have been spent getting caught up on work and doing some traveling and renovations to the home. Bathroom on the main floor was renovated and a bar was added – looks really nice. We ended up replacing the windows and door sliders on the deck as well – makes it so easy to open and close. We did get some ribbing for our urinal we put in the bathroom, but it looks nice and although it doesnt thrill the ladies, the guys love it ha. The best part we as we added A/C to house and what a difference that has made. So much easier to work from home when you are not sweating. Our home faces west towards the water and once the sun get’s overhead it is relentless. The new windows/sliders have a light tint that also has aided in keeping the place cool.
Last month we met mom in Denmark and took a Baltic cruise aboard the Norwegian Sun and visited Estonia, Berlin, Helsinki, Stockholm and St Petersberg. It was the first time we’d been back to Germany in 20 years. Prior to that we had spent a few days with friends in NY and saw my cousin perform on Broadway (Sister Act) and also Book of Mormon which swept the Tony Awards this year. Both were very funny.
Had a maintenance treatment on Monday which went well. As usual I arrived early (8am) for blood work and as seen by the doctor at 9:30am. She seemed pleased with how I’m doing and the numbers that came back from the blood test. Infusion started at about 10am and I was out cold from the Benadryl Drip (they give this to me before the Rituxin). When I woke up at 11, my buddy Mike was there and caught me by suprise. I found a pic he had taken of me with my phone catching flies (mouth open) while I was sleeping..nice work ha. The IV ended around 2pm and he drove me home – next treatment is Oct 24. This will go on every 8 weeks for the next 13 months. Not sure if I had shared this article before, but it looks to be positive. Rituxin is the biological agent I”ve been getting and the article deals with promising results by participating in the maintenance treatment that I’m currently doing. Obviously they stress in the article that what I have is an “incurable disease” but hopefully that will change in my lifetime.
I have yet to get that other website up and live, but once I do I will share the link.
ASCO 2009: Prolonged Rituximab Extends Remission in Follicular Lymphoma
June 16, 2009 (Orlando, Florida) — Rituximab (Rituxan) is widely used in the treatment of follicular lymphoma, and data from clinical trials show that the addition of rituximab to chemotherapy significantly improves outcomes, as previously reported by Medscape Oncology. Now results show that rituximab can have a profound effect on the disease, significantly extending disease remission in individuals with advanced-stage follicular lymphoma.
The long-term results come from a study that was initiated in 1998, published in 2004 (Blood 2004;103:4416-4423), and revisited in a presentation here at the American Society of Clinical Oncology 45th Annual Meeting. Lead author Michele Ghielmini, MD, from the Oncology Institute of Southern Switzerland in Bellinzona, explained that the team followed the surviving patients from this trial to investigate the proportion of long-term responders and the characteristics predicting a long-term response to rituximab.
They found that the benefit from rituximab is durable, said Jonathan Friedberg, MD, chief of hematology at the James P Wilmot Cancer Center, University of Rochester in New York. Follow-up is now 9.4 years, and 25% of those patients are still in remission at 8 years, he noted. In 1 subgroup of patients, nearly half were still in remission after 8 years.
In contemplating these results, Dr. Friedberg urged the audience to “keep in mind that follicular lymphoma is considered to be an incurable disease.”
But perhaps we are now giving some of these patients a chance toward a cure.
Speaking at a Highlights of the Day session, Dr. Friedberg said that this abstract was one of the most interesting of the whole meeting. “How can 4 additional doses given in the year after induction have such a profound effect 8 years later in a disease that is considered to be incurable?” he wondered.
“The rituximab era is only 12 years old and some of the trials have follow-up of only 5 years,” he said. “But perhaps we are now giving some of these patients a chance toward a cure.”
Long-Term Response Rates Evaluated
The original study was conducted in patients with newly diagnosed or refractory/relapsed follicular lymphoma. “The trial was for both chemotherapy-naïve and pretreated patients, and they received what was then the standard schedule for rituximab,” explained Dr. Ghielmini.
Of the 202 patients enrolled in the study, 151 were randomized. The median age of the patients was 57 years, 85% of the cohort had stage III or IV disease, 50% had bone marrow involvement, and two thirds had been previously treated with chemotherapy. All participants received rituximab at the standard dose of 375 mg/m2 weekly for 4 weeks, and were re-evaluated at week 12. Patients who responded to the therapy or who had stable disease were then randomized to either no further treatment, which was standard at that time (observation group; n = 78), or to 4 additional doses of rituximab given at 2-month intervals (extended-rituximab group; n = 73).
At a median follow-up of 8.9 years, among surviving patients who had been followed for at least 5 years, the median event-free survival (time to progression, relapse, second tumor, or death) was 13 months in the observation group and 24 months in the extended-rituximab group (P = .0012).
“I have been asked many times if these patients were really in need of further treatment, and we don’t really know because it was not mandatory in the protocol that patients be symptomatic,” said Dr. Ghielmini. “But two thirds of the patients were relapsing after chemotherapy, so in the majority of cases, these were patients who were in the need of treatment.”
Prolonged Schedule the Only Significant Prognostic Factor
The researchers also looked at prognostic factors that had been found to be significant in previous analyses. In univariate analysis, disease stage was important, especially for those who received the prolonged treatment. Patients with stage III disease did better than those with stage IV disease. The same held true for patients who were chemotherapy-naive and for those with a favorable Fc-receptor phenotype.
But in multivariate analysis at a median follow-up of 9.4 years, the only significant prognostic factor was the extended schedule (hazard ratio, 0.6; P = .007).
In a subanalysis, the researchers looked at the effect of response. “We hypothesized that patients who had stable disease following induction could take advantage of a longer treatment time with rituximab,” explained Dr. Ghielmini. “So we randomized patients with stable disease, but they did not gain very much from the prolonged rituximab treatment.”
Improved Survival in Responders and Chemotherapy-Naïve Patients
Instead, patients who had responded to induction had an important advantage. Among responding patients, the observation group experienced a 1 year remission, whereas those in the extended-rituximab group experienced a remission period of approximately 3 years. At 8 years, 35% of responders were still in remission.
Another subanalysis was conducted with a small group of chemotherapy-naïve patients (n = 38). After 8 years, 45% of these patients remained in remission, and this is the population targeted for the next clinical trial. “This is where we ask: Do they really need chemotherapy in the first line? We plan to offer patients randomization between single-agent rituximab [and] rituximab postchemotherapy,” he said.
The overall survival curve showed a difference between the 2 groups, even though it was not significant. But when the data from this trial were integrated with those from 3 other studies, the meta-analysis showed that there was an increase in overall survival with maintenance rituximab, compared with no maintenance, Dr. Ghielmini noted.
Most of the observed toxicity was acute or subacute, and the incidence of second malignancies was similar in the 2 groups: 12 patients in the observation group and 10 in the extended-rituximab group.
The data from this trial showed that prolonging treatment with rituximab improves outcomes and, on the basis of these results, the researchers hypothesized that extending treatment for an even longer period of time would have an even greater benefit. “We are running a similar trial, but this time we have randomized only the responders,” said Dr. Ghielmini. “They were randomized to 1 year of maintenance therapy vs 5 years of maintenance; so far we have recruited 270 patients.”
However, it is still too early to present any results, he added.
In a discussion of this paper, Ian W. Flinn, MD, PhD, director of Hematologic Malignancies Research at the Sarah Cannon Research Institute in Nashville, Tennessee, noted that in the 12 years since the introduction of rituximab, it has been shown to improve response rates in low-grade lymphoma when combined with chemotherapy.
“Not only does it improve response rates when added to chemotherapy, it improves progression-free survival and duration of responses,” said Dr. Flinn. “In some series, in some studies, and in some contexts, it has also improved overall survival.”
But like many studies, this paper raises more questions than can be answered from 1 database, he pointed out.
“Is rituximab useful after rituximab and chemotherapy? That question is not answered in the current dataset,” said Dr. Flinn. “The Swiss group is going to go on to see how long rituximab should be given after induction with chemotherapy or with rituximab.”
In addition, the optimal schedule for rituximab remains unknown. “In this study, the drug was given every 2 months for a total of 4 doses; some have used it every 3 months, and others have used 4 doses every 6 months,” he said. “These are still unanswered questions.”
The study was partially supported by Roche. Dr. Ghielmini reports receiving honoraria from Roche. Dr. Flinn reports receiving research support from Genentech. Dr. Friedberg reports acting as an advisor or consultant to Astellas, Eli Lilly, and Genentech, and receiving research funding from Cephalon, Millennium, and Rigel.
American Society of Clinical Oncology (ASCO) 45th Annual Meeting: Abstract 8512. Presented May 30, 2009