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> I have had mild to moderate Parkinson's for approx.10 years which has been > well controlled with Sinemet CR and Pergalide. > I recently begun a course of chemotherapy for carcinoma of the breast. > After my second lot of chemotherapy my Parkinson's seems to have become > much worse. Most of the time I can't walk. Increasing my medication doesn't > seem to help. I will have my last lot of chemotherapy in 4 weeks time. > Has anyone else had this experience? > Veronica Levin Veronica, I don't have an answer; but I did notice a report re chemotherapy-induced PD on the NPF forum recently, and I re-post it here for you, in case you would like to print it and discuss it with your doctor. Best, Kathrynne ================================================ Chemotherapy Induced Parkinsonism Responsive to Levodopa: An under-recognized Entity Cathy Chuang MD and others Movement Disorders 2003 volume 18, page 329 CASE 1 A 49-year-old woman was admitted with a 3-week course of progressive parkinsonism. Her past medical history was significant for breast cancer diagnosed 8 years previously and treated with a mastectomy and adjuvant chemotherapy. Cancer recurred 1 year before admission and she was treated unsuccessfully with multiple agents, including capecitabine, docetaxel, vinorelbine and tamoxifen. Six weeks before admission she began a regimen of weekly infusions of the antimetabolite gemacitabine. In addition to the above chemotherapeutic agents that were given over the past several months the only other medication she had taken was furosemide for upper extremity edema. She had no exposure to neuroleptics or any other dopamine receptor blocking agents, including anti-emetics. Three weeks later, she began to complain of generalized slowness drooling, softness of speech, and restlessness, and required increasing assistance with most daily activities. Examination revealed severe parkinsonism with 4+ bradykinesia and 3+ rigidity bilaterally, 3+ right, leg rest tremor, severe facial masking, hypophonia, and a shuffling gait with absent arm swing. Restlessness in the legs prompted her to pace frequently. Routine laboratory studies including blood counts and serum chemistries were normal, as was a magnetic resonance imaging (MRl) scan of the brain. A fluro-deoxyglucose-positron emission tomography (FDG-PET) scan showed globally reduced uptake, with focal reductions in the frontal and lateral temporal cortex and basal ganglia. A fluorodopa PET scan was recommended, but. the patient refused further testing Gemcitabine, which was last administered I week before admission, was immediately discontinued, and she was treated with Sinemet (carbidopa-levodopa), with dose increases up to 1,500 mg of levodopa per day. Within 2 to 3 days of levodopa treatment, her akathisia and parkinsonism began to improve; .she experienced wearing-off 'phenomena but no dyskinesias, she was also treated with lorazepam and temazepam for sleep difficulty and ondansetron for intermittent nausea. On follow-up evaluation 2 months later (on 1000 mg of levodopa/day). her parkinsonism had completely resolved, Levodopa was then discontinued 1 month later without any recurrence of parkinsonism. CASE 2 A 75-year-old woman with a history of chronic lymphocytic leukemia hypertension idiopathic pulmonary fibrosis, and metastatic squamous cell carcinoma of unknown primary received a course of treatment with carboplatin and paclitaxel 2 weeks before onset of parkinsonism. Two weeks later, she was hospitalized with acute respiratory distress and diagnosed with a deep vein thrombosis and pulmonary embolus. At the same time she developed severe slowing, tremor, and hypophonia. Her last dose of carboplatin and paclitaxel was 1 month before admission. The only other medication she had been taking was nifedipine. She had no exposure to neuroleptics or any other dopamine-rcceptor-blocking agents including antieimetics. A head computed tomography scan; blood counts and serum chemistries: and anti-Hu, antithyroglobulin, and antimicrosomal antibodies were normal. A brain MRI scan was only significant for mild atrophy and white matter ischemic disease. On examination, she had severe hypophonia and marked facial masking, bilateral cogwheel rigidity and bradykinesia. and resting and action tremor and myoclonic jerks and was unable to sit or stand without assistance. A modified barium swallow revealed severe oropharyngeal dysphagia and she was scheduled for placement of a feeding tube. In the interim, she was treated with levodopa increasing up to 1000 mg per day. Within 2 to 3 days, her parkinsonism and swallowing improved rapidly and dramatically, averting the need for enteral feeding. Ten days after admission, she was switched from carboplatin and paclitaxel to docetaxel. After 2 weeks of levodopa therapy, she was able to walk independently and feed herself. Parkinsonism although present, was markedly improved. Two months later, levodopa was discontinued and she remained free of any parkinsonian symptoms or signs when followed up 1 year later. CASE 3 A 60-year-old woman with a 2-year history of chronic myelogenous leukemia presented with a rest tremor of the face,tongue, and legs, Eight months before evaluation. she underwent a bone marrow transplantation for which she received high-dose cyclophosphamide, hydroxyurea and a-interferon. Three, months later, she developed an acute lymphoblastic leukemic transformation and was treated with high-dose busulfan, cyclophosphamide, and stem cell rescue. Her posttransplant course was complicated by acute renal failure, from which she recovered; pneumonia, which was treated with intravenous trimethoprim sulfamethoxozole and prednisone; and pansinusitis. which was treated with levonfloxacin. She did not have any exposure to neuroleptics or any other dopamine-receptor-blocking agents, including antiemetics. Approximately 4 months after her last course of chemotherapy, she developed a rest tremor of her chin and both legs, which decreased with action. Her medications at that time only included prednisone, ciprofloxacin, and hydroxyurea. Examination showed dysarthric speech, mild bradykinesia, minimal rigidity, stooped posture, and a shuffling gait with en bloc turns. She was treated with levodopa (600 mg/day), and tremor, speech, and gait difficulty improved within days. Two months later, levodopa was discontinued without recurrence of parkinsonism. DISCUSSION We describe 3 patients who developed acute or subacute parkinsonism after receiving chemotherapy. Signs of parkinsomsm included rest tremor, cogwheel rigidity, bradykinesia, and in the first 2 cases, postural impairment. Parkinsonism improved dramatically with levodopa, and parkinsonian signs spontaneously improved over weeks to months despite stable dosing of levodopa and eventual withdrawal of the drug. Our first 2 cases were similar in the severity of their parkinsonism and the rapid onset of symptoms after receiving chemotherapy. In the third case, onset of parkinsonism was delayed by 4 months and symptoms were less severe. There is precedent for such a delay in onset of parkinsonism after chemotherapy. Howell reported a patient with delayed-onset parkinsonism occurring 4-5 months after a course of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) A causal relationship between the chemotherapy and the parkinsonism was not proven, because the parkinsonism did not remit and, in fact, progressed despite discontinuation of chemotherapy. In contrast, symptoms and signs in our third patient were transient and resolved completely after discontinuation of levodopa, consistent with chemotherapy induced parkinsonism rather than idiopathic Parkinson's disease. The response to levodopa was dramatic in all 3 cases, and improvement in parkinsonism persisted even after levodopa was discontinued. The initial improvement was rapid and occurred within a few days after levodopa was started. We believe that this response was not solely secondary to withdrawal of the offending chemotherapeutic agent. In Cases 2 and 3, the, chemo therapeutic agents had been discontinued for 1 month and 4 months, respectively, but neither had any improvement of symptoms until levodopa therapy was begun. Therefore, we assert that the improvement in parkinsonism occurred as a result of a combination of levodopa therapy and the withdrawal of the offending agent. Our cases of chemotherapy-induced parkinsonism occurred after exposure to gemcitabine, carboplatin and paclitaxel, and cyclophosphamide and busulfan, agents that possess different mechanisms of action. Gemcitabine is a novel deoxycytidine analog similar to cytosine arabinose (ara-C) in the way it inhibits DNA polymerase. Carboplatin cross-links DNA, and paclitaxel stabilizes microtubules inhibiting mitosis. Both cyclophosphamide and busulfan act by alkylating and cross-linking DNA. Many other agents have been reported to cause a similar syndrome in single or multiple case reports (Table I). Cyclophosphamide and ara-C are the most commonly implicated agents, especially in combination with other chemotherapeutic agents before bone marrow transplantation. Other agents reported to cause parkinsonism include etoposide fluorouracil, vincristine and Adriamycin, doxorubicin, mitoxantrone, and methotrexate. The mechanism by which these drugs produce parkinsonism is unknown. Features suggesting a presynaptic nigrostriatal insult in our patients include the dramatic response to levodopa and the spontaneous remission of symptoms with time. That die deficits were reversible suggests the possibility that these agents cause parkinsonism by affecting the synthesis, packaging, or release of dopamine, rather than causing direct and irreversible degeneration of nigral neurons. In an analogous manner, the vinca alkaloids vincristine and vinblastine have been reported to decrease the plasma activity of dopamine b-hydroxylase, an enzyme that catalyzes norepinephrine synthesis. If this were true, one would expect to see decreased flurodopa uptake on a fluorodopa-PET scan obtained during the peak period of parkinsonism unfortunately, we were not able to obtain these scans. An FDG-PET scan in the first patient showed both cortical and subcortical impairment of glucose uptake consistent with diffuse cerebral injury (possibly related to her extensive history of prior treatment for cancer). However, despite this diffuse hypometabolism including the basal ganglia, this patient still had a response to levodopa, which suggests that there was a preservation of striatal dopamine receptors in the setting of a global toxic-metabolic insult. In summary, we present 3 patients with reversible, levodopa-responsive parkinsonism after treatment with chemotherapy. Prompt recognition and treatment of this condition may profoundly affect patients' quality of life. Parkinsonism, although uncommon, may be an underrecognized complication of cancer chemotherapy. -- Kathrynne Holden, MS, RD < [log in to unmask] > "Ask the Parkinson Dietitian" http://www.parkinson.org/ "Eat well, stay well with Parkinson's disease" "Parkinson's disease: Guidelines for Medical Nutrition Therapy" http://www.nutritionucanlivewith.com/ ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn