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The rarity of most primary skull base carcinomas and sarcomas has prevented a careful examination of the role of chemotherapy in these diseases. For advanced nasopharyngeal cancer, however, convincing data have now been generated supporting the role of systemic chemotherapy in conjunction with definitive locoregional treatment. Chemotherapy also seems to have a role in the management of other squamous cell head and neck cancers, and its use concurrently with radiation may be appropriate when extension to the base of the skull is identified. The role of chemotherapy in the management of the other skull base neoplasms remains less well established. Existing evidence is little more than anecdotal, and the use of systemic chemotherapy should generally be restricted to the palliative treatment setting. The ultimate role of this intervention in the aggressive sinonasal undifferentiated carcinomas and primary neuroendocrine carcinomas is unknown, but for these diseases, chemotherapy is a reasonable addition to locoregional treatment.

The results of several randomized trials suggest a marginal survival benefit for patients with metastatic non-small cell lung cancer after treatment with chemotherapy. This intervention, however, has not become standard therapy. Toxicity, cost, and inconvenience have led many physicians to question whether chemotherapy has even a palliative role in this disease. Furthermore, it is well established that patients with a poor performance status, who are most in need of symptomatic palliation, are also those who are least likely to benefit and most likely to experience treatment-related toxicity. Nonetheless, evidence of a symptomatic benefit from combination chemotherapy has been presented. Indeed, symptomatic palliation can result even in the absence of a conventionally defined chemotherapy-induced response. Phase III trials supporting the palliative value of chemotherapy, however, have been limited and inconclusive. Fortunately, other palliative treatment modalities exist. These interventions should be carefully integrated with chemotherapy when an overall treatment plan appropriate for an individual patient is being developed. In addition to the symptomatic needs of each individual, this treatment plan must also address both physician and patient biases.

The natural history of squamous cell head and neck cancer is well understood. Locoregional approaches to salvage therapy for this disease have curative potential, primarily because distant metastases are uncommon. Before proceeding with salvage treatment, however, clinicians should identify the extent of disease and determine whether the treatment intent is curative or palliative. Because of the associated morbidity, surgery should be considered only in patients for whom cure of recurrent disease is feasible. Radiation therapy may be indicated in patients whose disease recurs after surgery and in selected patients in whom initial radiation has failed. Single-agent and combination chemotherapy, in particular the combination of cisplatin and 5-fluorouracil, has achieved overall response rates of 30% to 40% in patients with recurrent disease. However, cure after salvage chemotherapy has not been achieved. Until salvage treatment regimens capable of achieving significant long-term survival are identified, symptomatic palliation will remain the main treatment goal in this patient population.

Eight patients presented with simultaneous multiple myeloma and acute renal failure requiring hemodialysis. Patients had no known pre-existing renal disease nor exposure to nephrotoxic agents or x-ray contrast dye. Renal failure was attributed to light chain nephropathy in all cases. In 4 of these patients the diagnosis of myeloma was initially unsuspected. Renal biopsies in 3 of these patients, and post-mortem material in a fourth revealed the changes of "myeloma kidney." No patient regained renal function and all required chronic hemodialysis. Among these eight patients, three survived for periods greater than 21 months.

Cisplatin (cis-diamminedichloroplatinum II), a chemotherapeutic agent used against epithelial neoplasms, is known to cause hypomagnesemia and renal magnesium wasting. In order to further characterize the effect of multiple doses of this drug upon serum magnesium levels and renal magnesium handling, we prospectively studied 28 patients who received a total of 82 doses of cisplatin. All patients developed hypomagnesemia that was dose-related (r = .66, P less than .001, n = 101); the lowest serum magnesium level reached in individual patients ranged from 0.3 to 1.7 mg/dL. Renal magnesium wasting was documented in 19 patients, with urinary fractional excretion of magnesium ranging from 2.9% to 22.3% despite serum magnesium levels of greater than or equal to 1.5 mg/dL. Evidence of renal tubular injury (renal tubular epithelial cells or tubular cell casts) was detected in 47 of 47 urine sediment examinations performed two to four days after cisplatin administration. There was no clear evidence that cisplatin caused defects in renal handling of electrolytes other than magnesium; in fact, 16 of the 28 patients demonstrated avid renal reabsorption of one or more other electrolytes despite significant magnesium wasting. We conclude that cisplatin alters renal tubular handling of magnesium, resulting in significant prolonged dose-related hypomagnesemia.