Ann Fonfa’s notes from Chemotherapy Foundation Symposium XIX November, 2001 One troubling note on a global scale - there was a handout entitled “Faculty Disclosure” which featured at least half the time, “will disclose at presentation”. I heard no such disclosures (although admittedly I was only present one and ½ days). Franco Muggia, MD Second-line Therapy of Ovarian Cancer: Doxirubicin, Topotecan or Both? Phase I/II 2nd line therapy showed oral topotecan to have an unacceptable level of toxicity when combined with Doxil. However, the first patient on the trial is now 3 years out and doing really well. “short infusions of topotecan are not optimal”. CA 125 showed doubling just before/ or as cancer progressed. Only 1 out of 88 was a false positive. The question is whether to treat or not? There was/is no proof that early treatment results in improved outcome. QOL is best w/o second line and may ruin chances for new therapies that are in clinical trials. Median survival after CA 125 rose was 13 months. From his abstract #31: “Industry-sponsored (pivotal) trials are designed to establish an indication for a particular drug. Accordingly, these trials attempt to select the appropriate conditions to prove the point: comparators are not what the regimens’ investigators might consider optimal, but rather those that have achieved a standard indication as determined by the U.S. Food and Drug Administration. In this context, the comparison of Doxil (Caelyx) with topotecan for second-line ovarian cancer (1) includes patients both platinum-resistant as well as potentially sensitive disease, and the results were expected to prove noninferiority in progression-free survival (PFS). Obviously, other drugs including platinum combinations play a role under similar circumstances. Nevertheless, the study emphasizes a number of findings that are important in relation to second-line therapy” “Currently, there is no evidence that combinations are better than single agents for salvage therapy, including retreatment with platinum-containing combinations. Our recent experience with the combination of both drugs and the results with Doxil in the study by Gordon et al (1) suggest that there is a subset of patients who have very long responses following Doxil or Doxil with topotecan.” 1) Gordon, A.N; Fleagle, J.T.;Guthrie, D.; et al. Interim Analysis of a Phase II Randomized Trial of Doxil/Caelyx (D) Versus Topotecan (T) in the Treatment of Patients with Relapsed Ovarian Cancer. Proc. Am. Soc. Clin. Oncol. 2000. 18 (abstract 1504) D.K. Armstrong, MD Long Term Treatment Strategies for Relapsed Ovarian Cancer: A Chronic Disease After looking at the ‘realities of what we have’, (we) may want to reconsider current ways of treatment. Should be looking at this as a chronic disease. The average patient will relapse after about two years. Using Taxol/Cisplatin, there was a steady relapse rate of 24-36 months. It is an oversimplification to say ‘resistant’ or not to platinum drugs. This is mostly useful in conducting trials. And most of those on trials are resistant since they recur earlier and are the usual study populations. Recurred patients rarely go into second remissions (complete responses are rare and short). “It should be appreciated that most of these patients will require therapy almost continuously for the remainder of their lives”. Toxicities naturally increase with continued therapy. “Therefore, the toxicities of therapy are paramount when considering treatment options”. The goal, not the cure, as it is not realistic in this (recurred) populations, is stable disease. Stable disease is associated with significant survival benefit. Overtreatment may be as dangerous and inappropriate as undertreatment when we consider the cumulative or late onset of toxicities from therapy. Does the patient understand that the goal is not curative? Is there a benefit for starting therapy based on rising/elevated CA 125? 20-25% do not show CA125 results. Weak secreters are found 1-2 months ahead of changes (almost the same time), moderate secreters about 6 months ahead and high secreters about 18 months ahead. (We) “do not have to treat patients as CA 125 rises”, patients may get a long time until disease actually progresses physically. The response to ‘salvage’ therapy increases with time. The ‘pros’ of early treatment include: Lower volume of disease Patients ‘think’ there is a better chance of cure ‘Cons’: Increased toxicity No better results due to resistance to platinum (seems true for taxanes too) Since those drugs with the highest response rate, topotecan, oral etoposide, liposomal doxirubicin, and gemcitabine, have similar response rates, the order may be more important than the drug used. Complications increase and are cumulative with topotecan. Therefore it may need to be used earlier. The more carboplatinum, the more myelosuppression. Doxil (liposomal) causes hand/foot syndrome which is different from peripheral neuropathy. There are cumulative toxicities from almost all chemos used. The patients need to set goals, be realistic, be informed so they can make decision, have some hope, use positive thinking and have the ability to cope. Allan Lipton, MD Zoledronic Acid in Lytic & Blastic Bone Metastases Dr. Lipton stated that Zoledronic Acid (zol) ‘does appear to be more effective” with prostate cancer patients, where pamidronate was not. Renal abnormalities was a problem with the 5 minute infusion, now 15 minutes is used. Here is some information from the abstract. The study compared zol to placebo in a randomized, Phase III double-‘masked’ study. The good news ”Zol demonstrated a significant advantage over placebo for median time to first skeletal-related event(SRE) (321 days for placebo vs. median ‘not achieved’ for zol 4 mg.) The effects were apparent early in this trial. At 3 months, only 12% of the zol-treated patients had experienced SRE while 23% of the placebo patients had one. At 6 months, it was 21% versus 31%. Bart Barlogie, MD Developmental Therapeutics for Multiple Myeloma: Road Map for the Future This talk was about thalidomide, recently shown to have ‘significant’ activity in refractory multiple myeloma. The good news is “ newer, more potent and less toxic derivatives of thalidomide are currently being evaluated”. In his talk, he stated that 40% of patients who had a complete response are still alive after 8 years (median of 3 years) with 20% ‘event-free’. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.