In order to potentiate the efficacy of antiemetic drugs such as metoclopramide (MCP) and the new drug GR 38032F, adjuvant antiemetic drugs such as benzodiazepines are used in cancer patients receiving chemotherapy. The purpose of our prospective study was to investigate the efficacy of alprazolam (APZ), a newer diazepam, as an adjuvant antiemetic drug, when combined with MCP, in carboplatin (JM8)-based chemotherapy. Thus, 42 patients entered this study. First they received only MCP 1 mg/kg in 15 min infusion (arm A). In the next cycle they received the combination of MCP in the same dose and a tablet of APZ 0.25 mg, 30 min before JM8 infusion and then 3.5, 5.5 and 11.5 h after (arm B). JM8 was administered alone (400 mg/m2) or in combination (300 mg/m2) with vinblastine (6 mg/m2), etoposide (100 mg/m2) or 5-fluorouracil (1,000 mg/m2). In arm A, according to the WHO classification, nausea was intense (p < 0.003) and the duration of nausea longer (p < 0.002). In arm B more patients did not present vomiting (p < 0.018). Secondary effects such as appetite (p < 0.04), diarrhea (p < 0.064), diaphoresis (p < 0.085) and headache (p < 0.024) were worst in arm A. We conclude that APZ increases the antiemetic effect of MCP on JM8. APZ is a useful adjuvant antiemetic drug, especially against the development of anticipatory anxiety, nausea and vomiting that many cancer patients presented during chemotherapy.
In 111 patients with ACC we studied CEA, FP, CA-125 and CA 19.9 during therapy and follow-up. Marker determination was performed every two months. CEA was elevated (> 5 ng/ml) in 82%, alpha FP (> 15 ng/ml) in 0%, CA-125 (> 38 U/ml) in 37%, CA 19.9 (> 30 U/ml) in 64% of the patients. We did not find significant differences between the sensitivity of CEA alone and that of the combination of CEA + CA-125 (86%), CEA + CA 19.9 (87%), CA-125 + CA-19.9 (71%) and CEA + CA-125 + CA 19.9 (88%). We did not find any correlation between the level of positivity of the markers and the clinical parameters we examined. When serial determinations were carried out, CEA showed the best indication of response to treatment, followed by CA 19.9. In the evaluation of the response to chemotherapy we found that CA 125 presented significant percentages of false-positive (9%) (P < 0.008) and false-negative (8.1%) (P < 0.008) results, compared to CEA and CA 19.9. CA 125 did not demonstrate any utility for the follow-up of patients with colorectal cancer although increased values were found in 37%. We conclude that CEA is currently the best marker for the follow-up of patients with colorectal cancer. The combination of CEA and CA 19.9 had some utility in follow-up, without significantly improving CEA results.
Forty-one patients with advanced renal cell cancer started treatment with recombinant alpha-interferon intramuscularly, beginning at a dose of 5 x 106 U x 3/week, progressively increasing doses every week, from 5 x 106 U x 3/week to 10 x 106 U x 3/ week, to the highest dose of 15 x 106 U x 3/week. No complete response was achieved, partial response was achieved in 6 (13%) patients with a median duration of 45.2 (13-134) weeks. The majority of side effects from interferon treatment evaluated according to WHO classification were seen during the first 2 months and they were fever (after interferon administration) in 95% patients, chills (51%), flu like syndrome (65%), fatigue (87%), anorexia (80%), worsening in performance status (56%), nausea and vomiting (19%), weight loss ( > 10% during therapy) (26%), leukopenia (14%), anemia (75%), neurological symptoms (43%), psychological symptoms (19%) and dyspnea (9%). The results are similar to other studies and toxicity was only moderate.
In a prospective randomized trial we compared the antiemetic efficacy of metoclopramide (MCP) and dexamethasone (DXM). A total of 172 patients receiving chemotherapy based on cisplatin 100 mg/m2/day were randomly allocated to four groups. CP was administered in 5 doses of 1.5 mg/kg (group A), 2 mg/kg (group C), or combined with 4 doses of DXM 4 mg/6 h (MCP: 1.5 mg/kg in group B; 2 mg/kg in group D). Vomiting was decreased in the DXM groups compared to groups A and C (p < 0.002), and the duratoin of nausea was greater in group A than in group D (P < 0.004). A greater disturbance in appetite was observed in group A compared to groups B (p < 0.028), D(p < 0.001) and C (p < 0.045). Activity problems were greater in group A than in C (p < 0.003) and D(p < 0.005). We noticed that a small increase in MCP (0.5 mg/kg) did not influence the antiemetic effect. The addition of DXM did not significantly alter the antiemetic results at the lower MCP dose, but improved them when MCP was slightly increased. We conclude that DXM slightly improves the antiemetic effect of MCP and the effects are related to the MCP dose.
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