Medication Summary
The agents described below are used in combination regimens, and doses are tailored to the histologic subtype of lymphoma and the stage of disease present.
In addition to the use of chemotherapeutic drugs, treatment also includes the employment of several classes of medications to support patients with non-Hodgkin lymphoma undergoing aggressive chemotherapy. These include the following:
-
Laxatives and stool softeners
-
Prophylactic antibiotics
-
Antiemetics
-
Antimucositic agents
-
Histamine (H2) receptor antagonists
-
Contraceptives
Prophylactic antibiotics
These medications include the following:
-
Trimethoprim-sulfamethoxazole (against Pneumocystis jiroveci [formerly, carinii])
-
Fluconazole (against Candida species)
-
Nystatin (against Candida species)
Antiemetics
Antiemetics include the following:
-
Serotonin (5-hydroxytryptamine type 3 [5-HT3]) receptor antagonists (ondansetron, granisetron, dolasetron)
-
Phenothiazine
-
Lorazepam
-
Metoclopramide
-
Dexamethasone
-
Tetrahydrocannabinol
Antimucositic agents
These agents include the following:
-
Saline or bicarbonate rinse
-
Biotene rinse
-
Peridex rinse
-
Glutamine suspension
Histamine (H2) receptor antagonists
Famotidine and ranitidine help to prevent gastritis in patients receiving high-dose corticosteroids.
Contraceptives
Oral or injectable contraceptives can be used to suppress menses in female adolescents at risk for menorrhagia due to thrombocytopenia.
Antineoplastics, Other
Class Summary
Cancer chemotherapy is based on an understanding of tumoral cell growth and on how drugs affect this growth. After cells divide, they enter a period of growth (ie, phase G1), followed by deoxyribonucleic acid (DNA) synthesis (ie, phase S). The next phase is the premitotic phase (ie, G2), followed by mitotic cell division (ie, phase M).
Cell division rates vary for different tumors. Most common cancers grow slowly compared with normal tissues, and the growth rate may further decrease in large tumors. This difference allows normal cells to recover from chemotherapy more quickly than malignant cells do and is the rationale for current cyclic dosage schedules.
Antineoplastic agents interfere with cell reproduction. Some agents are cell cycle specific, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not phase specific.
Cellular apoptosis (ie, programmed cell death) is another potential mechanism of many antineoplastic agents.
Daunorubicin (Cerubidine)
Daunorubicin is an anthracycline. Its multiple mechanisms of action involve DNA intercalation, topoisomerase-mediated DNA strand breakage, and oxidative damage due to free radical production.
Doxorubicin (Adriamycin)
Doxorubicin is an anthracycline. Its multiple mechanisms of action involve DNA intercalation, topoisomerase-mediated DNA strand breakage, and oxidative damage due to free radical production.
Cytarabine
Cytarabine is an antimetabolite. A cytotoxic analogue of deoxycytidine, it interferes with DNA replication and repair by incorporating into DNA and inhibiting DNA polymerase.
6-mercaptopurine (6-MP, Purinethol)
This agent is a purine analog. Its metabolites are incorporated into DNA, inhibiting synthesis.
6-thioguanine (Tabloid)
This drug is a purine analogue. Its metabolites are incorporated into DNA, inhibiting synthesis
Methotrexate (Trexall)
Methotrexate is a cytotoxic folate antagonist. It inhibits dihydrofolate reductase.
Vincristine (Vincasar PFS)
Vincristine inhibits microtubule formation in the mitotic spindle, causing metaphase arrest.
Etoposide (VP-16, Toposar)
Etoposide inhibits topoisomerase, causing DNA strand breaks.
Cyclophosphamide
Cyclophosphamide alkylates and cross-links DNA.
Ifosfamide (Ifex)
Ifosfamide alkylates and cross-links DNA.
Carmustine (Gliadel, BiCNU)
Carmustine alkylates DNA and ribonucleic acid (RNA). It may also act by carbamoylation of enzymes.
L-asparaginase (Elspar)
L-asparaginase is an enzyme produced by Escherichia coli that catalyzes the conversion of L-asparagine to aspartic acid. L-asparagine is a nonessential amino acid for most normal tissues. Many lymphoid malignancies have low levels of asparagine synthase and, therefore, depend on the circulating pool of L-asparagine.
Nelarabine (Arranon)
Nelarabine is a prodrug of the deoxyguanosine analogue 9-beta-D-arabinofuranosylguanine (ara-G). It is converted to active 5'-triphosphate (ara-GTP), a T-cell–selective nucleoside analog. Leukemic blast cells accumulate ara-GTP, allowing for its incorporation into DNA; the result is inhibition of DNA synthesis and cell death.
Nelarabine has been approved by the US Food and Drug Administration (FDA) as an orphan drug to treat T-cell lymphoblastic lymphoma that is not responsive or is relapsing with at least 2 chemotherapy regimens.
Hydroxyurea (Hydrea, Droxia)
Hydroxyurea apparently inhibits DNA synthesis.
PD-1/PD-L1 Inhibitors
Pembrolizumab (Keytruda)
Indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
Corticosteroids
Class Summary
Corticosteroids elicit anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.
Methylprednisolone (Medrol, A-Methapred, Solu-Medrol)
The mechanism of cytotoxicity for methylprednisolone is unknown, but it is apparently mediated by glucocorticoid receptors.
Dexamethasone (Baycadron)
The mechanism of cytotoxicity for dexamethasone is unknown, but it is apparently mediated by glucocorticoid receptors. The drug's action is apparently enhanced by CNS penetration (relative to prednisone).
Antibiotics, Other
Class Summary
Therapy should cover all likely pathogens in the context of this clinical setting.
Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra DS)
Trimethoprim/sulfamethoxazole inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. The antibacterial activity of trimethoprim/sulfamethoxazole includes Pneumocystis jiroveci.
Antifungals
Class Summary
These agents may change the permeability of the fungal cell resulting in a fungicidal effect.
Fluconazole (Diflucan)
Fluconazole is a synthetic oral antifungal agent (a broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation.
Nystatin
Nystatin is a fungicidal and fungistatic antibiotic obtained from Streptomyces noursei. It is effective against candidal organisms. It changes the permeability of the fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak.
Antiemetic Agents
Class Summary
Antiemetics are always prescribed before and after the administration of chemotherapy, for the prevention of chemotherapy-induced nausea and vomiting.
Ondansetron (Zofran, Zuplenz)
Ondansetron is a selective 5-HT3 receptor antagonist that blocks serotonin peripherally and centrally. It prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin) and whole-body radiotherapy.
Granisetron (Kytril, Granisol, Sancuso)
At the chemoreceptor trigger zone, granisetron blocks serotonin centrally and peripherally on vagal nerve terminals.
Palonosetron (Aloxi)
Palonosetron, is a selective 5-HT3 receptor antagonist with a long half-life (40 h). It is a selective 5-HT3 receptor antagonist that blocks serotonin peripherally and centrally. It prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin) and whole-body radiotherapy.
Dolasetron (Anzemet)
At the chemoreceptor trigger zone, granisetron blocks serotonin centrally and peripherally on vagal nerve terminals.
Metoclopramide (Reglan, Metozolv)
The antiemetic effect of metoclopramide appears to be due to its ability to block dopamine receptors in the chemoreceptor trigger zone (CTZ) of the central nervous system (CNS). This agent also enhances gastrointestinal motility and accelerates gastric emptying time.
Lorazepam (Ativan)
Lorazepam is a benzodiazepine used as an antiemetic in patients receiving chemotherapy for non-Hodgkin disease. By increasing the action of gamma-aminobutyric acid (GABA) the major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the CNS, including the limbic system and the reticular formation.
Chlorpromazine
The antiemetic effect of metoclopramide appears to be due to its ability to block dopamine receptors in the chemoreceptor trigger zone (CTZ) of the central nervous system (CNS).
Dronabinol
This agent inhibits endorphins in the brain's emetic center through an unknown mechanism.
Histamine H2 Antagonists
Class Summary
Like antacids, these agents decrease the amount of acid in the refluxate by inhibiting acid production. These agents are used to help prevent gastritis in patients receiving high-dose corticosteroids. All H2 -receptor antagonists are equipotent when used in equivalent doses. H2 -receptor antagonists are considered the drugs of choice for children because pediatric doses are well established and the medications are available in liquid form.
Nizatidine (Axid)
Nizatidine competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reductions in gastric acid secretion, gastric volume, and hydrogen concentrations.
Ranitidine (Zantac)
Ranitidine inhibits histamine stimulation of the H2 receptor in gastric parietal cells, reducing gastric acid secretion, gastric volume, and hydrogen ion concentrations.
Famotidine (Pepcid)
Famotidine competitively inhibits histamine at the H2 receptors of gastric parietal cells, reducing gastric acid secretion, gastric volume, and hydrogen ion concentrations.
Progestins
Class Summary
These agents may induce endometrial thinning by inhibiting the secretion of pituitary gonadotropins.
Norethindrone acetate (Aygestin, Camila, Errin)
Norethindrone is a common progestin used in many of the oral contraceptive pills currently available. Progestins stop endometrial cell proliferation, allowing organized sloughing of cells after withdrawal. These agents typically do not stop acute bleeding episode, but they produce normal bleeding episodes following withdrawal.
Medroxyprogesterone (Depo-Provera, Provera)
Progestins stop endometrial cell proliferation, allowing organized sloughing of cells after withdrawal. These agents typically do not stop acute bleeding episode, but they produce normal bleeding episodes following withdrawal.
Medroxyprogesterone is a common progestin available in both an oral and an intramuscular depo form. The efficacy and adverse effects of this drug are similar to those of norethindrone.
Estrogens/Progestins
Class Summary
Oral contraceptives may be used to decrease the amount of bleeding. Topical preparations can be used to help strengthen the mucosa and decrease its susceptibility to bleeding. Before use, screening tests for pulmonary AVMs should be performed because of the risk of complications involving thromboembolism.
Norethindrone acetate and ethinyl estradiol (Aranelle, Balziva, Nortrel, Loestrin 1.5/30)
Norethindrone acetate and ethinyl estradiol are used to decrease mucosal bleeding. The combination probably works by strengthening mucosal tissues and thereby making them more resistant to bleeding.
Uricosuric Agents
Class Summary
These agents control hyperuricemia and are used to attempt to prevent urate nephropathy and subsequent oliguric renal failure.
Allopurinol inhibits xanthine oxidase, thereby reducing uric acid. The IV form (Aloprim) may be used for patients unable to tolerate oral administration.
Caution is necessary because of the high uric acid concentration in the urine. In the presence of allopurinol, the excretion of uric acid, xanthine, and hypoxanthine increases several hundred fold, enough to exceed their solubility limit in the renal tubules even at a urinary pH level of 7. Also, at a urinary pH level higher than 7.5, crystallization of hypoxanthine may occur, which necessitates withdrawal of bicarbonate from IV fluids.
Allopurinol (Zyloprim, Alloprim)
Allopurinol inhibits xanthine oxidase, the enzyme that synthesizes uric acid from hypoxanthine and xanthine, thus decreasing production and excretion of uric acid and increasing the levels of more soluble xanthine and hypoxanthine. The drug reduces the synthesis of uric acid without disrupting the biosynthesis of vital purines. Patient response is measured by serum uric acid levels assessed at 48 hours after the initiation of therapy. Dosage adjustments are made as needed.
Rasburicase (Elitek)
Rasburicase is a recombinant form of the enzyme urate oxidase, which oxidizes uric acid to allantoin. It is indicated for the treatment and prophylaxis of severe hyperuricemia associated with the treatment of malignancy. Hyperuricemia causes a precipitant in the kidneys, which leads to acute renal failure. Unlike uric acid, allantoin is soluble and easily excreted by the kidneys. The elimination half-life for rasburicase is 18 hours.
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Massive mediastinal T-lymphoblastic lymphoma. Note compression of the left mainstem bronchus and the pulmonary atelectasis.
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Non-Hodgkin lymphoma of the terminal ileum. Note the doughnut sign, ie, intraluminal contrast material surrounded by a grossly thickened bowel wall. This appearance is highly suggestive of small noncleaved cell lymphoma (Burkitt type).
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Malignant pleural effusion. Non-Hodgkin lymphoma of the terminal ileum was diagnosed; the doughnut sign (ie, intraluminal contrast material surrounded by a grossly thickened bowel wall) was present. A diagnosis of stage 3 Burkitt lymphoma was established by means of pleurocentesis. (The bone marrow was normal.) The patient was treated successfully and never required an abdominal procedure.
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Massive left pleural effusion as a complication of an upper anterior mediastinal T-lymphoblastic lymphoma. Note the atelectatic left lung. The diagnosis was established by means of thoracentesis. This patient had presented with bilateral parotid gland enlargement.
Tables
- Table 1. Modified LSA2 L2 Therapy in Children's Cancer Group Protocol 552
- Table 2. Therapy for Stage III and IV Non–B-Cell Disease* According to BFM Protocol 86
- Table 3. Clinical Risk Groups in the International Trial for Patients With SNCCL (Children's Cancer Group study 5961)
- Table 4. Standard Therapy in the International Trial for Patients With SNCCL, Group A*
- Table 5. Standard Therapy in the International Trial for Patients With SNCCL, Group B*
- Table 6. Standard Therapy in the International Trial for Patients With SNCCL, Group C*
- Table 7. Prephase Therapy for Ki-1+ Anaplastic LCLs According to the ALCL99 Protocol
- Table 8. Subsequent Therapy for Ki-1+ Anaplastic LCLs According to the ALCL99 Protocol (alternating cycles, repeated 3times each)
Phase |
Drug |
Route |
|
Induction |
Cyclophosphamide, vincristine, daunorubicin |
IV |
|
Ara-C, methotrexate |
IT |
||
Prednisone |
PO |
||
Consolidation |
Ara-C |
IV or SC |
|
6-thioguanine |
PO |
||
Methotrexate |
IT |
||
L-asparaginase |
IM |
||
BCNU |
IV |
||
Phase |
Cycle |
Drug |
Route |
Maintenance* |
1 |
6-thioguanine |
PO |
Cyclophosphamide |
IV |
||
2 |
Hydroxyurea |
PO |
|
Daunorubicin |
IV |
||
3 |
Methotrexate |
PO |
|
BCNU |
IV |
||
4 |
Ara-C |
IV or SC |
|
Vincristine |
IV |
||
Source: Children's Cancer Group Ara-C = cytarabine; BCNU = 1,3-bis(2-chloroethyl)-1-nitrosourea, or carmustine; IM = intramuscular; IT = intrathecal; IV = intravenous; PO = oral; SC = subcutaneous * A minimum of 5 repeated courses (total duration of therapy >18 mo) are noted. Each course of intrathecal methotrexate (day 0 of each course) consists of 4 cycles of rotating drug pairs that are administered every 2 weeks after blood counts have recovered. |
|||
Phases |
Drug |
Route |
Induction |
Prednisone, 6-mercaptopurine |
PO |
Vincristine, daunorubicin, cyclophosphamide, Ara-C |
IV |
|
L-asparaginase |
IM |
|
Methotrexate |
IT |
|
Consolidation |
6-mercaptopurine |
PO |
Methotrexate with leucovorin rescue |
IV |
|
Methotrexate |
IT |
|
Re-induction |
Dexamethasone, 6-thioguanine |
PO |
Vincristine, doxorubicin, cyclophosphamide, Ara-C |
IV |
|
L-asparaginase |
IM |
|
Methotrexate |
IT |
|
Maintenance† |
6-mercaptopurine, methotrexate |
PO |
Source: Berlin-Frankfurt-Munster Group Ara-C = cytarabine; IT = intrathecal; IV = intravenous; PO = oral; SC = subcutaneous * Diagnoses included lymphoblastic lymphoma of the T-cell or precursor B-cell type, immunoblastic T-cell lymphoma, and other peripheral T-cell lymphomas. Of note, patients with Ki-1+ anaplastic large cell lymphomas (LCLs) were not included. † Continued until 24 months after diagnosis. |
||
Clinical Group |
Subjects, Estimated % |
Definition |
A |
10 |
All resected stage I or abdominal stage II tumors |
B |
65 |
Unresected stage I or II tumor, stage III, tumor, or stage IV tumor with no CNS involvement and < 25% marrow blasts |
C |
25 |
CNS involvement or >25% marrow blasts |
Drug |
Route |
Prednisone |
PO |
Vincristine, cyclophosphamide, doxorubicin |
IV |
Filgrastim (G-CSF), to enhance neutrophil recovery |
SC or IV |
G-CSF = granulocyte colony-stimulating factor; IV = intravenous; PO = oral; SC = subcutaneous * See Table 3 for the definition of group A. All subjects received 2 cycles. |
|
Phase |
Drug |
Route |
|
Reduction |
Prednisone |
PO |
|
|
Vincristine, cyclophosphamide |
IV |
|
|
Methotrexate/hydrocortisone |
IT |
|
Phase |
Cycles |
Drug |
Route |
Induction |
2, starting 7 days after reduction |
Prednisone |
PO |
Vincristine, methotrexate with leucovorin rescue, cyclophosphamide, doxorubicin |
IV |
||
Methotrexate/hydrocortisone |
IT |
||
Filgrastim (G-CSF) |
SC or IV |
||
Consolidation |
2 |
Methotrexate with leucovorin rescue, Ara-C |
|
Methotrexate/hydrocortisone, Ara-C/hydrocortisone |
|
||
Filgrastim (G-CSF) |
|
||
Maintenance** |
1 |
Prednisone |
PO |
Vincristine, methotrexate with leucovorin rescue, cyclophosphamide, doxorubicin |
IV |
||
Methotrexate/hydrocortisone |
IT |
||
Ara-C = cytarabine; G-CSF = granulocyte colony-stimulating factor; IT = intrathecal; IV = intravenous; PO = oral, SC = subcutaneous * See Table 3 for the definition of group B. |
|||
Phase |
Drug |
Route |
|
Reduction |
Prednisone |
PO |
|
Vincristine, cyclophosphamide |
IV |
||
Methotrexate/Ara-C/hydrocortisone |
IT |
||
Induction, cycle 1 starting 7 days after reduction |
Prednisone |
PO |
|
Vincristine, high-dose methotrexate with leucovorin rescue, cyclophosphamide, doxorubicin |
IV |
||
Methotrexate/Ara-C/hydrocortisone |
IT |
||
Filgrastim (G-CSF) |
SC or IV |
||
Induction, cycle 2 |
Prednisone |
PO |
|
Vincristine, high-dose methotrexate with leucovorin rescue, cyclophosphamide, doxorubicin |
IV |
||
Methotrexate/Ara-C/hydrocortisone |
IT |
||
Filgrastim (G-CSF) |
SC or IV |
||
Consolidation, 2 cycles† |
High-dose Ara-C, etoposide (VP-16) |
IV |
|
Filgrastim (G-CSF), days 7-21 |
SC or IV |
||
High-dose methotrexate with leucovorin rescue |
IV |
||
Methotrexate/Ara-C/hydrocortisone |
IT |
||
Maintenance 1 |
Prednisone |
PO |
|
Vincristine, high-dose methotrexate with leucovorin rescue, cyclophosphamide, doxorubicin |
IV |
||
Methotrexate/Ara-C/hydrocortisone |
IT |
||
Maintenance 2 |
Ara-C, etoposide (VP-16) |
IT |
|
Maintenance 3 |
Prednisone |
PO |
|
Vincristine, cyclophosphamide, doxorubicin |
IV |
||
Maintenance 4 |
Ara-C, etoposide (VP-16) |
IV |
|
Ara-C = cytarabine; G-CSF = granulocyte colony-stimulating factor; IT = intrathecal; IV = intravenous; PO = oral, SC = subcutaneous * See Table 3 for the definition of group C. † For patients with CNS involvement, during consolidation cycle 1 only. |
|||
Drug |
Route |
Dexamethasone |
PO |
Cyclophosphamide |
IV |
Methotrexate/Ara-C/prednisolone |
IT |
Ara-C = cytarabine; IT = intrathecal; IV = intravenous; PO = oral. |
|
Cycle |
Drug |
Route |
|
A |
Dexamethasone |
PO |
|
Methotrexate with leucovorin rescue, ifosfamide, etoposide (VP-16), Ara-C |
IV |
||
B |
Dexamethasone |
PO |
|
Methotrexate with leucovorin rescue, cyclophosphamide, doxorubicin |
IV |
||
Ara-C = cytarabine; IT = intrathecal; IV = intravenous; PO = oral. |
|||
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- Overview
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- Treatment
- Approach Considerations
- Tumor Lysis Syndrome Treatment
- Chemotherapy for Lymphoblastic Lymphoma
- Chemotherapy for Small Noncleaved Cell Lymphoma
- Chemotherapy for Large Cell Lymphoma
- Radiation Therapy
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