Chemotherapy with cisplatin and 5-fluorouracil for penile and urethral squamous cell carcinomas

Article Abstract:

Squamous cell cancers of the penis and male urethra are sufficiently uncommon that there has been little opportunity to arrive at a consensus about optimal treatment. The survival rate is 50 to 70 percent for those patients in whom the cancer has not spread to neighboring lymph nodes. However, for patients with node involvement, the 5-year survival rate drops to 10 to 30 percent despite radiotherapy or surgery. Numerous chemotherapeutic regimens have been reported for penile cancer, but differences among the patients and the small numbers of patients make comparison of the regimens difficult. Among the agents reported to be effective against penile cancer is cisplatin. Because cisplatin and 5-fluorouracil have synergistic effects, the combination was used in the treatment of five patients with squamous cell carcinoma of the penis and one with squamous cell carcinoma of the urethra. A sequential protocol was used, as this is believed to reduce the suppressive effects on the bone marrow. A cycle of chemotherapy consisted of 100 milligrams of cisplatin per meter squared, with extensive use of antiemetics. On the second day, 40 milligrams 5-fluorouracil per meter squared was infused hourly for 120 hours, or until mucous inflammation occurred. This cycle was repeated every three to four weeks. Although mild side effects occurred, no dose modification was needed for any patient. The patient with urethral cancer achieved complete response, but microscopic examination revealed lymph node involvement which was ultimately treated with the same chemotherapy combined with radiotherapy. He has now had 32 months of complete remission. The patients with penile carcinoma achieved partial responses; their survival time from original diagnosis ranged from 13 to 26 months. It should be noted that the combination of cisplatin and 5-fluorouracil showed antitumor activity when used to treat recurrences, as well as when used in the initial treatment. A combination of surgery and chemotherapy may result in prolonged disease-free survival in cases of penile and urethral squamous cell carcinoma. (Consumer Summary produced by Reliance Medical Information, Inc.)

Urinary tract cancer, Urologic cancer, Penile cancer

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Induction chemotherapy with a new regimen alternating cisplatin, fluorouracil with mitomycin, hydroxyurea and bleomycin in carcinomas of nasopharynx or other sites of the head and neck region

Article Abstract:

Surgery and radiotherapy are the standard treatments for squamous cell carcinoma of the head and neck. Unfortunately, a cure rate of less than 20 percent may be expected, due largely to the fact that squamous cell carcinoma of the head and neck has usually advanced to Stage III or Stage IV before it is diagnosed. In recent years, induction chemotherapy was explored in an effort to improve the survival of patients with squamous cell carcinoma of the head and neck, and encouraging rates of complete response, ranging from 20 to 54 percent, have been reported. To continue the exploration of the potential benefits of induction chemotherapy in the treatment of this cancer, an alternating protocol was used in the treatment of 66 patients with locally advanced (Stages III and IV) squamous cell carcinoma of the head and neck. The regimen consisted of three cycles of continuous infusion of cisplatin and 5-fluorouracil with three cycles of mitomycin, hydroxyurea, and bleomycin. The cycles of mitomycin, hydroxyurea, and bleomycin may be given on an outpatient basis, which not only reduces hospital time, but may minimize undesirable side effects as well. The patients who completed the induction chemotherapy were then given standard radiotherapeutic treatment; seven were also treated surgically. A complete response was observed in 20 percent of the patients, and a partial response was seen in 50 percent. Sixty-one percent of the patients remain alive at 24 months. The regimen seems effective, and, in combination with radiotherapy, may result in a cure for some patients. However, the rate of response observed suggests that the alternating therapy is probably not superior to chemotherapy with cisplatin and 5-fluorouracil alone. (Consumer Summary produced by Reliance Medical Information, Inc.)

Methods, Hydroxyurea, Mitomycin, Bleomycin

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A Phase I, II study of high-dose 5-fluorouracil and high-dose leucovorin with low-dose phosphonacetyl-L-aspartic acid in patients with advanced malignancies

Article Abstract:

An understanding of the mechanisms of action of chemotherapeutic agents can lead to improvements in their effectiveness. 5-fluorouracil is an analog of the natural pyrimidine uracil. Both substances are modified in a series of metabolic steps and then incorporated into molecules of RNA. For uridine, the process is natural, for 5-fluorouracil, the process is pathological and may kill the cell. One example of how another drug might influence the effectiveness of a chemotherapeutic agent is PALA, or N-phosphonacetyl-L-aspartic acid. PALA depletes UTP (uridine triphosphate) within cells. The less normal UTP is available, the more likely the pathological 5-fluoro derivative is to become incorporated into RNA. (To be sure, this is not the only metabolic effect of PALA.) A study was conducted in which PALA was added to a chemotherapeutic protocol of 5-fluorouracil (5-FU) and leucovorin (LV). The 27 evaluable patients all had advanced cancer for which the majority had received previous treatment. Adverse side effects prevented several patients from tolerating the full intended dose of 5-FU. Of the 18 patients who received larger doses, 9 experienced responses. There was only one complete response; this occurred in a patient with pancreatic cancer who had been previously untreated. It is worth noting that three of the four patients with colorectal cancer who responded to treatment had previously received chemotherapeutic regimens also containing 5-fluorouracil. A response was also observed in one patient with lung cancer who had previously received cisplatin, mitomycin, and etoposide, and in one breast cancer patient for whom cyclophosphamide, doxorubicin, and 5-FU had been previously ineffective. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cancer, Metastasis, Cancer metastasis, Leucovorin, Folinic acid

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