20th April 2002
Harry:
Our child's protocol included a drug related to fludarabine [ARA-C] and we did encounter several significant problems. However, these problems did clear as the drug cleared the body. The major and most common concern is kidney damage, including gout and kidney stone formation. This was handled by administering allopurinol until all of the drug was cleared. At one point during the therapy our child was also receiving a full litre of IV fluids each hour, every hour for a full 24 hours. [Not fun and very tiring as unable to sleep for more than 40 minutes at a time because of hourly IV changes and having to go to the bathroom every hour.]
Another serious side effect we encountered - and quite rare according to the sci/med literature - was the almost complete and very rapid loss of vision. This cleared because the HEM/ONC stopped the drug immediately upon identification of this side-effect. This occurred only during the second round this drug. Essentially, this means that you should always monitor for side-effects.
Below is a cut & paste from drugs.com [my preferred drug database/site]. Suggest you print this.
"Geriatrics
Although appropriate studies on the relationship of age to the effects of fludarabine have not been performed in the geriatric population, clinical trials have included elderly patients and geriatrics-specific problems that would limit the usefulness of this medication in the elderly are not expected . However, elderly patients are more likely to have age-related renal function impairment, which may require reduction of dosage in patients receiving fludarabine.
"Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate) - not necessarily inclusive ( = major clinical significance):
"Note:
Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
"Allopurinol or Colchicine or Probenecid or Sulfinpyrazone
(fludarabine may raise the concentration of blood uric acid as part of a tumor lysis syndrome;
dosage adjustment of antigout agents may be necessary to control hyperuricemia and gout;
allopurinol may be preferred to prevent or reverse fludarabine-induced hyperuricemia because of risk of uric acid nephropathy with uricosuric antigout agents)
"Blood dyscrasia-causing medications (see Appendix II )
(leukopenic and/or thrombocytopenic effects of fludarabine may be increased with concurrent or recent therapy if these medications cause the same effects;
dosage adjustment of fludarabine, if necessary, should be based on blood counts)
"Bone marrow depressants, other (see Appendix II ) or Radiation therapy
(additive bone marrow depression may occur;
dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively)
"Pentostatin
(concurrent use with fludarabine is not recommended because of a possible increased risk of fatal pulmonary toxicity )
"Vaccines, killed virus -
(because normal defense mechanisms may be suppressed by fludarabine therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors;
estimates vary from 3 months to 1 year)
"Vaccines, live virus -
(because normal defense mechanisms may be suppressed by fludarabine therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine;
immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the fludarabine therapy. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors;
estimates vary from 3 months to 1 year. Patients with leukemia in remission should not receive live virus vaccine until at least 3 months after their last chemotherapy. In addition, immunization with oral poliovirus vaccine should be postponed in persons in close contact with the patient, especially family members)
"Laboratory value alterations -
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate) - not necessarily inclusive ( = major clinical significance):
With physiology/laboratory test values Alkaline phosphatase and Aspartate aminotransferase (AST [SGOT]) ( serum values may rarely be increased )
Uric acid concentrations in blood and urine
(may be increased as part of a tumor lysis syndrome in patients with large tumor burdens )
"Medical considerations/Contraindications -
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate) - not necessarily inclusive ( = major clinical significance).
Risk-benefit should be considered when the following medical problems exist Bone marrow depression
(lower dosage may be necessary )
Chickenpox, existing or recent (including recent exposure) or Herpes zoster (risk of severe generalized disease)
Gout, history of or Urate renal stones, history of
(risk of hyperuricemia as part of a tumor lysis syndrome in patients with large tumor burdens )
Infection Renal function impairment(reduced elimination; dosage adjustment may be necessary )
Sensitivity to fludarabine Caution should be used also in patients who have had previous cytotoxic drug therapy or radiation therapy.
"Patient monitoring
The following are especially important in patient monitoring (other tests may be warranted in some patients, depending on condition;
= major clinical significance):
Hematocrit or hemoglobin and Leukocyte count, total and, if appropriate, differential and Platelet count
(determinations recommended prior to initiation of therapy and at periodic intervals during therapy;
frequency varies according to clinical state, agent, dose, and other agents being used concurrently )
Uric acid concentrations, serum
(recommended prior to initiation of therapy and at periodic intervals during therapy in patients with large tumor burdens, because of the risk of tumor lysis syndrome; frequency varies according to clinical state, agent, dose, and other agents being used concurrently )"
Also suggest that you look up ACOR.org [Association of Cancer Online Resources]. This is a non-profit organization and has email groups, including specific patient groups for different leukemias, lymphomas, etc. This group continues to be very useful for us since we can ask and exchange information with other patients [or their parents] with similar diagnoses. A lot of the time one just doesn't know whether a symptom should be discussed with the HEM/ONC or not. By discussing it with others in similar circumstances, you can get a better perspective. Also very useful for learning about different treatment options.
Another worthwhile site is OncoLink [at U. Penn] - this has detailed information on all of the different leukemias. The few articles I've read on hairy cell leukemia often discuss an enlarged spleen - an indicator of this cancer's progression.
Here are some links for you:
Treatment/articles on hairy cell leukemia:
[url="http://cancer.med.upenn.edu/templates/types/article.cfm?c=8&s=31&ss=248&id=7290#2"]http://cancer.med.upenn.edu/templates/types/article.cfm?c=8&s=31&ss=248&id=7290#2[/url]
OncoLink Home Page:
[url="http://cancer.med.upenn.edu/"]http://cancer.med.upenn.edu/[/url]
I haven't run a drug interaction on your sister's meds [using drugs.com] yet as I need to log off shortly. However, most of the major interactions are covered in the cut & paste.
The fatigue, etc. may be a consequence of the leukemia, the drugs or other things. This is very hard to tell unless the person is being very closely monitored and every detail is recorded. Fludarabine does inhibit the immune system so some of your sister's pre-existing immune-related conditions [unassociated with the leukemia] may change while she's on this regimen. Has her doctor mentioned anything about this?
Will check for your response/questions later this weekend.
Regards,
Jay
Our child's protocol included a drug related to fludarabine [ARA-C] and we did encounter several significant problems. However, these problems did clear as the drug cleared the body. The major and most common concern is kidney damage, including gout and kidney stone formation. This was handled by administering allopurinol until all of the drug was cleared. At one point during the therapy our child was also receiving a full litre of IV fluids each hour, every hour for a full 24 hours. [Not fun and very tiring as unable to sleep for more than 40 minutes at a time because of hourly IV changes and having to go to the bathroom every hour.]
Another serious side effect we encountered - and quite rare according to the sci/med literature - was the almost complete and very rapid loss of vision. This cleared because the HEM/ONC stopped the drug immediately upon identification of this side-effect. This occurred only during the second round this drug. Essentially, this means that you should always monitor for side-effects.
Below is a cut & paste from drugs.com [my preferred drug database/site]. Suggest you print this.
"Geriatrics
Although appropriate studies on the relationship of age to the effects of fludarabine have not been performed in the geriatric population, clinical trials have included elderly patients and geriatrics-specific problems that would limit the usefulness of this medication in the elderly are not expected . However, elderly patients are more likely to have age-related renal function impairment, which may require reduction of dosage in patients receiving fludarabine.
"Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate) - not necessarily inclusive ( = major clinical significance):
"Note:
Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
"Allopurinol or Colchicine or Probenecid or Sulfinpyrazone
(fludarabine may raise the concentration of blood uric acid as part of a tumor lysis syndrome;
dosage adjustment of antigout agents may be necessary to control hyperuricemia and gout;
allopurinol may be preferred to prevent or reverse fludarabine-induced hyperuricemia because of risk of uric acid nephropathy with uricosuric antigout agents)
"Blood dyscrasia-causing medications (see Appendix II )
(leukopenic and/or thrombocytopenic effects of fludarabine may be increased with concurrent or recent therapy if these medications cause the same effects;
dosage adjustment of fludarabine, if necessary, should be based on blood counts)
"Bone marrow depressants, other (see Appendix II ) or Radiation therapy
(additive bone marrow depression may occur;
dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively)
"Pentostatin
(concurrent use with fludarabine is not recommended because of a possible increased risk of fatal pulmonary toxicity )
"Vaccines, killed virus -
(because normal defense mechanisms may be suppressed by fludarabine therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors;
estimates vary from 3 months to 1 year)
"Vaccines, live virus -
(because normal defense mechanisms may be suppressed by fludarabine therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine;
immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the fludarabine therapy. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors;
estimates vary from 3 months to 1 year. Patients with leukemia in remission should not receive live virus vaccine until at least 3 months after their last chemotherapy. In addition, immunization with oral poliovirus vaccine should be postponed in persons in close contact with the patient, especially family members)
"Laboratory value alterations -
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate) - not necessarily inclusive ( = major clinical significance):
With physiology/laboratory test values Alkaline phosphatase and Aspartate aminotransferase (AST [SGOT]) ( serum values may rarely be increased )
Uric acid concentrations in blood and urine
(may be increased as part of a tumor lysis syndrome in patients with large tumor burdens )
"Medical considerations/Contraindications -
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate) - not necessarily inclusive ( = major clinical significance).
Risk-benefit should be considered when the following medical problems exist Bone marrow depression
(lower dosage may be necessary )
Chickenpox, existing or recent (including recent exposure) or Herpes zoster (risk of severe generalized disease)
Gout, history of or Urate renal stones, history of
(risk of hyperuricemia as part of a tumor lysis syndrome in patients with large tumor burdens )
Infection Renal function impairment(reduced elimination; dosage adjustment may be necessary )
Sensitivity to fludarabine Caution should be used also in patients who have had previous cytotoxic drug therapy or radiation therapy.
"Patient monitoring
The following are especially important in patient monitoring (other tests may be warranted in some patients, depending on condition;
= major clinical significance):
Hematocrit or hemoglobin and Leukocyte count, total and, if appropriate, differential and Platelet count
(determinations recommended prior to initiation of therapy and at periodic intervals during therapy;
frequency varies according to clinical state, agent, dose, and other agents being used concurrently )
Uric acid concentrations, serum
(recommended prior to initiation of therapy and at periodic intervals during therapy in patients with large tumor burdens, because of the risk of tumor lysis syndrome; frequency varies according to clinical state, agent, dose, and other agents being used concurrently )"
Also suggest that you look up ACOR.org [Association of Cancer Online Resources]. This is a non-profit organization and has email groups, including specific patient groups for different leukemias, lymphomas, etc. This group continues to be very useful for us since we can ask and exchange information with other patients [or their parents] with similar diagnoses. A lot of the time one just doesn't know whether a symptom should be discussed with the HEM/ONC or not. By discussing it with others in similar circumstances, you can get a better perspective. Also very useful for learning about different treatment options.
Another worthwhile site is OncoLink [at U. Penn] - this has detailed information on all of the different leukemias. The few articles I've read on hairy cell leukemia often discuss an enlarged spleen - an indicator of this cancer's progression.
Here are some links for you:
Treatment/articles on hairy cell leukemia:
[url="http://cancer.med.upenn.edu/templates/types/article.cfm?c=8&s=31&ss=248&id=7290#2"]http://cancer.med.upenn.edu/templates/types/article.cfm?c=8&s=31&ss=248&id=7290#2[/url]
OncoLink Home Page:
[url="http://cancer.med.upenn.edu/"]http://cancer.med.upenn.edu/[/url]
I haven't run a drug interaction on your sister's meds [using drugs.com] yet as I need to log off shortly. However, most of the major interactions are covered in the cut & paste.
The fatigue, etc. may be a consequence of the leukemia, the drugs or other things. This is very hard to tell unless the person is being very closely monitored and every detail is recorded. Fludarabine does inhibit the immune system so some of your sister's pre-existing immune-related conditions [unassociated with the leukemia] may change while she's on this regimen. Has her doctor mentioned anything about this?
Will check for your response/questions later this weekend.
Regards,
Jay