Chemotherapy dosing

High-risk neuroblastoma is a childhood malignancy with a poor prognosis. Gradual improvements in survival have correlated with therapeutic intensity, and the ability to harvest, process and store autologous hematopoietic stem cells has allowed for dose intensification beyond marrow tolerance.

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Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fuoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice.

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Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Radiation Oncology cung cấp cho các bạn kiến thức về ngành y đề tài: " Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer...

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Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Radiation Oncology cung cấp cho các bạn kiến thức về ngành y đề tài: " Chemotherapy followed by low dose radiotherapy in childhood Hodgkin's disease: retrospective analysis of results and prognostic factors...

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Interferon Before imatinib, when allogeneic SCT was not feasible, IFN-α therapy was the treatment of choice. Only longer follow-up of patients treated with imatinib will prove whether IFN-α will still have a role in the treatment of CML. Its mode(s) of action in CML is still unknown. Chemotherapy Initial management of patients with chemotherapy is currently reserved for rapid lowering of WBCs, reduction of symptoms, and reversal of symptomatic splenomegaly. Hydroxyurea, a ribonucleotide reductase inhibitor, induces rapid disease control.

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Because a number of patients with diffuse large B cell lymphoma are either initially refractory to therapy or relapse after apparently effective chemotherapy, 30–40% of patients will be candidates for salvage treatment at some point. Alternative combination chemotherapy regimens can induce complete remission in as many as 50% of these patients, but long-term disease-free survival is seen in ≤10%.

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Myelodysplasia: Treatment The therapy of MDS has been unsatisfactory. Only stem cell transplantation offers cure: survival rates of 50% at 3 years have been reported, but older patients are particularly prone to develop treatment-related mortality and morbidity. Results of transplant using matched unrelated donors are comparable, although most series contain younger and more highly selected cases.

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Stages I and II Seminoma Inguinal orchiectomy followed by retroperitoneal radiation therapy cures ~98% of patients with stage I seminoma. The dose of radiation therapy (2500– 3000 cGy) is low and well tolerated, and the in-field recurrence rate is negligible. About 2% of patients relapse with supradiaphragmatic or systemic disease. Surveillance has been proposed as an option, and studies have shown that about 15% of patients relapse. The median time to relapse is 12–15 months, and late relapses (5 years) may be more frequent than with nonseminoma.

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One approach—so-called neoadjuvant chemotherapy—involves the administration of adjuvant therapy before definitive surgery and radiation therapy. Because the objective response rates of patients with breast cancer to systemic therapy in this setting exceed 75%, many patients will be "downstaged" and may become candidates for breast-conserving therapy. However, overall survival has not been improved using this approach.

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Chemotherapy The chemotherapy combination most widely used for SCLC is etoposide plus cisplatin or carboplatin, given every 3 weeks on an outpatient basis for four to six cycles. Increased dose intensity of chemotherapy adds toxicity without clear survival benefit. Appropriate supportive care (antiemetics, fluid support with cisplatin, monitoring of blood counts and blood chemistries, monitoring for signs of bleeding or infection, and, as required, use of hematopoietins) and adjustment of chemotherapy doses on the basis of nadir granulocyte counts are essential.

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The level of suspicion of infections with certain organisms should depend on the type of cancer diagnosed (Table 82-3). Diagnosis of multiple myeloma or CLL should alert the clinician to the possibility of hypogammaglobulinemia. While immunoglobulin replacement therapy can be effective, in most cases prophylactic antibiotics are a cheaper, more convenient method of eliminating bacterial infections in CLL patients with hypogammaglobulinemia.

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Mucositis Irritation and inflammation of the mucous membranes particularly afflicting the oral and anal mucosa, but potentially involving the gastrointestinal tract, may accompany cytotoxic chemotherapy. Mucositis is due to damage to the proliferating cells at the base of the mucosal squamous epithelia or in the intestinal crypts. Topical therapies, including anesthetics and barrier-creating preparations, may provide symptomatic relief in mild cases.

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Primary prophylaxis (i.e., shortly after completing chemotherapy to reduce the nadir) of G-CSF to patients receiving cytotoxic regimens is associated with a 20% incidence of febrile neutropenia. "Dose-dense" regimens, where cycling of chemotherapy is intended to be completed without delay of administered doses, may also benefit, but such patients should be on a clinical trial. Administration of G-CSF in these circumstances has reduced the incidence of febrile neutropenia in several studies by about 50%.

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Table 81-2 Commonly Used Cancer Chemotherapy Agents Drug Exam ples of Usual Doses Toxicity Issues Interactions, Direct DNA-Interacting Agents Alkylators Cyclophospha 2000 400– mg/m2 Marrow (relative Liver metabolism required mide IV platelet sparing) to activate to phosphoramide 100 mg/m2 PO qd Common alkylatora Mesna protects Cardiac dose) against Cystitis mustard + acrolein (high "high-dose" bladder damage Mechloretha mine 6 mg/m2 IV day Marrow Topical use in cutaneous lymphoma Vesicant 1 and day 8 Nausea Chlorambucil 1–3 mg/m2 qd PO Marrow Common alkylatora ...

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Principles of Chemotherapy Medical oncology is the subspecialty of internal medicine that cares for and designs treatment approaches to patients with cancer, in conjunction with surgical and radiation oncologists. The core skills of the medical oncologist include the use of drugs that may have a beneficial effect on the natural history of the patient's illness or favorably influence the patient's quality of life. In general, the curability of a tumor is inversely related to tumor volume and directly related to drug dose.

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Application to Patients Teletherapy Radiation therapy can be used alone or together with chemotherapy to produce cure of localized tumors and control of the primary site of disease in tumors that have disseminated. Therapy is planned based on the use of a simulator with the treatment field or fields designed to accommodate an individual patient's anatomic features. Individualized treatment planning employs lead shielding tailored to shape the field and limit the radiation exposure of normal tissue. Often the radiation is delivered from two or three different positions.

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