Considering longer chemotherapy

       The newest prognosis for cancer may be longer chemotherapy.Doctors and pharmaceutical companies are moving towards treating cancer patients with drugs continuously, even when they may not urgently need them. That would be a departure from the common practice of stopping treatment when the cancer is under control and resuming it only if the cancer worsens.
       The strategy is called maintenance therapy - akin to periodic tune-ups aimed at preventing a car from breaking down. Doctors say it could prolong the time that tumours are under control,helping to turn cancer into a chronic disease that is kept in check even if it is not cured.
       While maintenance therapy is not entirely new, its use is growing, in part because some of the newer cancer drugs are more tolerable than the toxic ones of old and can be taken for longer periods.
       At the recent annual meeting of the American Society of Clinical Oncology,for instance, doctors filled a huge auditorium for a debate on whether it is time to adopt maintenance therapy for lung cancer, the nation's leading cause of cancer death. Other cancers for which maintenance therapy is being used or tried include ovarian cancer, multiple myeloma and non-Hodgkin's lymphoma.
       But some experts say that in many cases, the longer-term use of drugs has not been proved to prolong life.
       Instead, it may just subject cancer patients to more side effects and tens of thousands of dollars in extra costs. There is also concern that tumours might become resistant to a drug used for a long time.
       "Generally more is better, in both dose and potentially duration," said Dr Susan L. Kelley, chief medical officer of the Multiple Myeloma Research Foundation, which sponsors research on treatments for that disease. However, she said,"there are numerous kinds of cost to the patient, to the health system, to give these drugs over the longer term."
       Dr Lawrence H. Einhorn, a professor at Indiana University, said much of the push for maintenance therapy was coming from pharmaceutical companies,which want their drugs "to be used as early as possible and as long as possible".
       And executives of these companies acknowledge that the therapy would mean bigger sales."This is clearly a game-changing opportunity," Brian P.Gill, vice-president for corporate communications at Celgene, which is testing its drug Revlimid for maintenance treatment of multiple myeloma, told investors at a conference in March.
       But the executives, and many doctors,say there is a good rationale for maintenance therapy.
       Although treatment varies with the type of cancer, many patients now receive several initial cycles of chemotherapy.Then, if the cancer goes into remission,or even if the tumour simply stops growing, the therapy is stopped. It is resumed,usually with different drugs, only when the cancer starts worsening again.
       That strategy evolved in part because the older chemotherapy drugs were so toxic that patients often needed to take a holiday from treatment.
       "But if you think about it practically,you don't really want to give the tumour a holiday," said Colin Goddard, the chief executive of OSI Pharmaceuticals, which is trying to position its lung cancer drug Tarceva for use in maintenance therapy.
       Some cancer patients welcome, or even demand, maintenance therapy,wanting to keep up the fight against their disease.
       "I was one of those people who was frightened to stop chemo," said Barbara Platzer,71, of St Louis, who has ovarian cancer.
       So when her initial six cycles of chemotherapy ended with her cancer in remission, she enrolled in a clinical trial that provided her with 12 monthly maintenance treatments of an experimental drug called Xyotax. The results of the trial are not yet known, but Platzer's cancer has remained in remission.
       But Caryl Castleberry of Glen Ellen,California, who also has ovarian cancer,turned down maintenance therapy.
       "I could hardly wait to be free from treatment, so the extra year they suggested was just not acceptable," said Castleberry,61, whose cancer has nonetheless remained in remission for six years.
       Dr Robert L. Coleman, an expert on ovarian cancer at the M.D. Anderson Cancer Centre in Houston, said that because relapses tend to be fatal, there has been an urgent effort to prevent or delay them. But over the years, eight maintenance therapies failed in clinical trials.
       Finally, a study published in 2003 showed that 12 monthly maintenance treatments of paclitaxel, a generic drug whose brand name is Taxol, delayed tumour progression by about seven months as compared with three monthly treatments with the same drug. But the difference in survival was not statistically significant, Dr Coleman said, so there is still some debate about the merits of maintenance therapy for ovarian cancer.
       For lung cancer, the move to maintenance therapy is being spurred by the results of a clinical trial of the drug Alimta that were presented at the oncology meeting in Orlando, Florida, in late May.Based on that trial, both the Food and Drug Administration and European regulators approved the use of Alimta for maintenance therapy earlier this month.
       The trial, sponsored by Eli Lilly, which makes Alimta, involved 663 patients with advanced cancer whose tumours had shrunk or remained stable after the customary four cycles of initial chemotherapy. In typical practice, those patients would not be treated again unless their tumours resumed growing.
       But in the trial, some patients got Alimta immediately after completing the initial, or first-line, chemotherapy. They lived a median of 13.4 months, significantly longer than the 10.6 months for those who got a placebo. And patients with the type of tumour for which Alimta works best lived a median of 15.5 months with maintenance therapy.
       "This will change the treatment paradigm," said Dr Chandra P. Belani, deputy director of the Penn State Hershey Cancer Institute and the lead investigator in the trial.
       But sceptics said the trial did not directly compare giving Alimta immediately with waiting until the tumour worsened. So it is not clear whether it was just the drug that provided the benefit, rather than the maintenance therapy.Two-thirds of the patients in the placebo group did get second-line therapy when their tumours worsened, but usually not with Alimta.
       Alimta, also known as pemetrexed,costs about $4,000(136,000 baht) per infusion given once every three weeks.Based on data from Lilly's trials, patients getting the drug as maintenance therapy would receive an average of three more infusions than those getting the drug as second-line therapy.
       Also, about 30 to 50 percent of lung cancer patients never get second-line chemotherapy, often because their condition worsens too much. So if Alimta were used as maintenance therapy, many more patients would get it.
       For non-Hodgkin's lymphoma, the drug used for maintenance is usually Rituxan, or rituximab, which is sold by Genentech and Biogen Idec.
       A clinical trial showed that maintenance therapy with Rituxan did not help patients with an aggressive form of the disease. But a separate study, published recently in The Journal of Clinical Oncology , showed that it helped those with less aggressive forms of the disease.
       After three years, cancer had not worsened for 68 percent of those who received the maintenance therapy. That was true for only 33 percent of those who did not receive the therapy. The survival difference was smaller, with 92 percent of those who got the maintenance therapy alive after three years compared with 86 percent of those who did not.
       "We need more follow-up to see if it will improve overall survival," said Dr Thomas M. Habermann of the Mayo Clinic, an author of the study. Nevertheless, many doctors are giving patients maintenance treatment, usually four weekly infusions of Rituxan every six months for two years. That would cost about $30,000(1 million baht) a year.
       For multiple myeloma, the drug being tried most often for maintenance therapy - Revlimid, or lenalidomide - is already being used for patients with relapses. It costs more than $6,000(204,000 baht) a month and is taken as a once-a-day pill,making it particularly convenient for long-term use.
       Right now it is used for an average of 10 months in the United States; with maintenance therapy that could grow to years, since remissions for multiple myeloma can last that long.
       Trials are under way, but some doctors are not waiting."We really need some randomised data to support it, but in the meantime it seems like a good idea,"said Dr Brian G.M. Durie, chairman of the International Myeloma Foundation,an advocacy and research group that gets some financing from pharmaceutical companies.
       Kevin, a graduate student with multiple myeloma, says he hoped a stem cell transplant would mark the end of his treatment. So he was taken aback when his doctor suggested taking Revlimid for two years as maintenance therapy as part of a clinical trial. He has been taking it a year so far, with some mild side effects like fatigue.
       "I'm not enthusiastic about being on a drug like this indefinitely," he said."But on the other hand, it's a lot better than relapse."