Antitumor therapy is provided to control cancer-related symptoms and prolong survival, thus optimizing quality of life. Many adult cancers are responsive to chemotherapy (
Figure 1), and such treatment improves numerous symptoms (
Figure 2).
4 Tumor response to chemotherapy has been shown to correlate with improvement of symptoms. For example, a combination treatment regimen combining irinotecan hydrochloride with cisplatin for esophageal cancer was shown to have a response rate of 57% with associated improvement in dysphagia in 35 patients.
5-7 A recent study in patients with ovarian cancer showed that chemotherapy can improve overall survival and cancer-related symptoms.
8
Even without evidence of tumor response to chemotherapy, patients can clinically benefit. In those with pancreatic cancer, gemcitabine hydrochloride did not prolong life; however, its use was associated with less requirement for analgesics and improvement in patient function.
9
Cytotoxic drugs used in palliative chemotherapy attack cells during cell division; these agents are phase-specific and cycle-specific. Phase-specific drugs terminate cells only if given during a certain phase of the cell cycle. Prolonging treatment increases the number of cells killed because dividing cells cycle at random; it is therefore a reasonable approach.
Cycle-specific drugs target cells during any phase of division; thus, higher doses kill more cells than lower doses. Cytotoxic drugs can also be classified according to their specific cellular mode of action. Antimetabolites (5-fluorouracil, fludarabine phosphate, methotrexate, gemcitabine) interfere with the incorporation of nucleic acid bases into DNA; their activity peaks during the S phase of the cell cycle. Alkylating drugs (cyclophosphamide, ifosfamide, chlorambucil, melphalan, cisplatin, carboplatin) form linkages between the strands of DNA that prevent this biogenic substance from separating during the M phase of the cell cycle.
Antitumor antibiotics (bleomycin, doxorubicin hydrochloride, epirubicin hydrochloride) typically interfere with binding of base-pair molecules and prevent separation of DNA strands during the M phase of the cell cycle. Plant alkaloids act as either mitotic spindle inhibitors (vincristine, vinblastine, paclitaxel) or topoisomerase inhibitors (topotecan hydrochloride, irinotecan, and etoposide).
10
Given the potential toxicities of chemotherapeutic agents, it is critical to educate patients about their illness and to discuss their expectations of treatment. Many drugs are available for palliation, and it is important to be aware of their potential adverse effects (
Figure 3). Ideal candidates for palliative treatment are patients with excellent performance status (a measure of a patient's functional capacity) and tumor sensitivity to chemotherapy. Use of an evaluation tool such as the Karnofsky scale enables assessment of a patient's ability to accomplish self-care activities (
Table).
10 A patient with clinically significant comorbidities and poor functional status will have difficulty tolerating treatment and may become more disabled.
The most challenging issue for both patient and physician is balancing symptom relief against treatment toxicity. When adverse effects of palliative chemotherapy begin to cause a decline in performance status, physicians must reconsider treatment and patient goals. Working together as a team, the patient, family, and physician can make the best decision.
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