Carlo Basurto

Predictive factors of delayed emesis in cisplatin-treated patients and antiemetic activity and tolerability of metoclopramide or dexamethasone : a randomized single-blind study

To prevent delayed emesis induced by cisplatin (mean dose 90 mg/m2), 120 consecutive patients were randomized to receive, in a 7-day crossover design, oral metoclopramide (20 mg q.i.d.), dexamethasone (1 mg q.i.d.) or placebo (two tablets q.i.d.) starting 24 hours after the end of chemotherapy. Complete protection from nausea, but not from vomiting. was significantly increased by both dexamethasone and metoclopramide with respect to placebo. Important prognostic factors favoring the appearance of delayed emesis were incomplete protection from vomiting during the first 24 hours after cisplatin, female gender, and highest cisplatin doses. Tolerability of both drugs was good. Larger and randomized controlled trials are necessary to identify better preventive treatment of delayed emesis induced by cisplatin.

Evaluation of serum HER2 extracellular domain in early breast cancer patients: correlation with clinicopathological parameters and survival

BACKGROUND We explored the correlation between serum human epidermal growth factor receptor-2 (HER2) extracellular domain (ECD) and tissue HER2 status, their relationship with clinicopathological parameters and their impact on disease-free survival (DFS) and overall survival in early breast cancer patients. PATIENTS AND METHODS This prospective trial included patients with stage I-III breast cancer. Serum HER2 ECD levels were measured by two enzyme-linked immunosorbent assays before surgical treatment. Tissue HER2 status was analyzed by immunohistochemistry (IHC) in all tumors; FISH assay was utilized in HER2 2+ tumors by IHC. RESULTS From May 2000 to July 2005, 256 consecutive stage I-III breast cancer patients were included in this study. High serum HER2 ECD levels (>or=15 ng/ml) were reported in 23 patients (9.0%) and HER2-positive status in tumor tissue was observed in 42 patients (16.4%) with a concordance of 87.1%. High HER2 ECD levels were significantly associated with high histological grade (P = 0.003), stage III (P = 0.008), lymph node involvement (P = 0.035) and negativity of both estrogen (P = 0.016) and progesterone (P = 0.007) receptors. At multivariate analysis, high serum HER2 ECD levels were a significant independent prognostic factor of worse DFS (P = 0.009). CONCLUSIONS A statistically significant association was observed between high serum HER2 ECD levels and worse DFS in early breast cancer patients.

Assessment of nausea

SummaryIn a standardized way three different methods of measuring nausea have been assessed in 849 patients enrolled in 4 double blind, randomized, clinical trials, and 2 observational studies. Nausea was measured before and 2, 4, 6, 8 and 24 hours after cancer chemotherapy by using a discrete scale (DS), a visual analogue scale (VAS) and a continuous chromatic analogue scale (ACCS), and it was evaluated according to 4 different dimensions: maximal intensity (MI) entity (E) duration (D) and quantity (Q).The distributions of nausea measurements in the population, agreement between the scales and their sensitivity, and agreement between dimensions and their sensitivity were analyzed.A uniform distribution of nausea measurements was found only in patients receiving chemotherapy without any antiemetic treatment. There was substantial equivalence of the different scales, and no advantage was shown an using an analogue (VAS) than a discrete (DS) scale.A trend toward increasing sensitivity in detecting differences as the dimensions of nausea considered became more inclusive of the various aspects of this symptom (Q more sensible than E more sensible than MI) was observed.

A pilot study of metoclopramide, dexamethasone, diphenhydramine and acupuncture in women treated with cisplatin.

SummaryA total of 26 women who submitted to cisplatin chemotherapy received as antiemetic treatment a combination of metoclopramide, dexamethasone and diphenhydramine. Acupuncture according to traditional Chinese medicine was also carried out. The results were compared with those obtained in a similar group of women with cancer, who were treated in the same setting with the same antiemetic combination but without additional acupuncture. Acupuncture was shown to increase complete protection from nausea and to decrease the intensity and duration of nausea and vomiting. However, the difficulties of performing acupuncture routinely in daily practice are a hindrance to its wider use.

Double-blind crossover trial of single vs. divided dose of metoclopramide in a combined regimen for treatment of cisplatin-induced emesis

In a double-blind crossover antiemetic study in cisplatin-treated cancer patients, metoclopramide 4 mg/kg as a single intravenous dose (regimen A) was compared with 3 mg/kg in two doses (regimen B). In both regimens, metoclopramide was combined with dexamethasone and diphenhydramine. 65 consecutive, chemotherapy-naïve inpatients (45 males and 20 females) treated with high doses (at least 50 mg/m2) of cisplatin entered the study and 54 completed both treatments. Complete protection from vomiting and nausea, mean number of emetic episodes, mean maximum intensity of nausea and mean duration of emesis or nausea were similar with the two antiemetic regimens. 23 patients (43%) did not express a treatment preference, while 16 (30%) preferred regimen B and 15 (28%) preferred regimen A. Side-effects were similar with the two metoclopramide schedules. A combined antiemetic regimen of a single high dose of metoclopramide (4 mg/kg) can preserve efficacy and tolerability and thus should be preferred.

A double-blind trial comparing antiemetic efficacy and toxicity of metoclopramide versus methylprednisolone versus domperidone in patients receiving doxorubicin chemotherapy alone or in combination with other antiblastic agents.

Nausea and vomiting are reported in ∼60% of neoplastic patients treated with doxorubicin used alone at doses ≥50 mg/m2 or in combination with other noncisplatin antiblastic agents. In a double-blind study we compared the efficacy and tolerability of metoclopramide (MTC) versus Domperidone (DMP) versus methylprednisolone (MP) administered intravenously (i.v.) to inpatients. Forty-four patients entered the trial. The three antiemetic regimens were found equally effective. A complete protection from vomiting/nausea was obtained in 14/11 (93.3%/73.3%) of patients treated with MTC, in 15/14 (100%/93%) of those treated with MP and in 11/11 (78.6%/78.6%) of those treated with DMP. Side effects were slight and not significantly different among the three regimens. In conclusion, i.v. MTC and MP (DMP is no longer available in i.v. formulation) as single agents are an adequate treatment for prevention of nausea and vomiting induced by doxorubicin alone or in combination with other noncisplatin antiblastic agents.

Weekly paclitaxel in metastatic breast cancer patients: a phase II study.

Aims and background Paclitaxel, a microtubule inhibitor, is one of the most active drugs in metastatic breast cancer. A weekly schedule, at a median dose-intensity of 91 mg/m2, is effective and has less side effects than a 3-week schedule. In this phase II study, we evaluated the toxicity and the activity of weekly 1 hr paclitaxel infusions in metastatic breast cancer patients. Study design Between February 1999 and February 2001, 26 patients with metastatic breast cancer were treated with weekly paclitaxel (60–90 mg/m2/1 hour iv infusion/weekly). The treatment was planned to continue until disease progression or prohibitive toxicity; in patients with responsive or stable disease, paclitaxel was stopped after 6 months of therapy. Results At a median follow-up of 18.7 months (range, 6.8–30.8), all patients are assessable for response and toxicity. We obtained 8 partial responses (30.8%), 8 stable disease (30.8%) and 10 disease progression (38.4.%). The overall response was 30.8% (95% CI, 13.1–48.5). The median duration of response was 7.6 months (range, 1.8–12.4); median time to progression was 4.86 months (range, 1.4–12.4); median overall survival was 9.9 months (range, 1.7–29.2+). Treatment was well tolerated. Hematological toxicity was mild and only one patient developed grade 3 anemia. Two patients experienced grade 3 cardiovascular toxicity; both had received anthracycline-based regimens. Conclusions In our experience, weekly administration of paclitaxel shows a substantial degree of activity even in pretreated metastatic breast cancer patients. The toxicity profile is favorable.

Double-blind controlled trial of the antiemetic efficacy and toxicity of methylprednisolone (MP), metoclopramide (MTC) and domperidone (DMP) in breast cancer patients treated with i.v. CMF

Sixty-two patients treated for the first time with i.v. CMF were included in a double-blind comparative study aimed at evaluating the efficacy of 3 different drugs (methylprednisolone (MP), metoclopramide (MTC), and domperidone (DMP) in preventing chemotherapy-induced nausea and vomiting. Complete protection from vomiting/nausea was obtained in 85%/80% in the group treated with MP; in 60%/65% in the group treated with MTC and in 38%/42% in the group treated with DMP. Average number of vomiting episodes was 2.4 with MP, and 1.7 with MTC and 6.2 with DMP. Older patients seem to be a prognostically unfavorable subgroup. Side-effects were mild and infrequent. We conclude that MP and MTC are probably equally efficacious antiemetic treatments in patients undergoing i.v. CMF chemotherapy, but due to the risk of extrapyramidal reactions with MTC, MP probably should be the treatment of choice in these patients.

A Prospective Randomized Double-Blind Crossover Study Comparing the Antiemetic Activity of Alizapride and Metoclopramide in Patients Receiving Cisplatin Chemotherapy

We designed a double-blind randomized crossover study to compare the antiemetic activity and toxicity of high-dose intravenous alizapride (3.5 mg/kg) versus high-dose intravenous metoclopramide (1 mg/kg) both combined with intravenous methylprednisolone in 40 untreated cancer patients submitted to cisplatin chemotherapy alone. The mean number of vomiting episodes (3.6 vs. 1.0), length of vomiting (209.8 vs. 80.9 min), and rate of complete prevention of vomiting (25% vs. 68.4%) at first cycle were in favor of metoclopramide, with a statistically significant difference. This difference was not statistically significant in the second cycle after crossover. Toxicity of both treatments was mild and diarrhea was more frequent in the alizapride-treated patients. Preference expressed by the patients was also in favor of metoclopramide. We conclude that alizapride offers less antiemetic protection than metoclopramide in patients receiving cisplatin chemotherapy. Further use of alizapride in such patients is not recommended.

Salvage chemotherapy in metastatic breast cancer: An experience with the combination of mitoxantrone, 5-fluorouracil, and L-leucovorin

SummaryFrom January 1992 to July 1993, 28 patients with metastatic breast cancer were entered in a phase II trial to assess the activity and toxicity of the combination of mitoxantrone, 5-fluoruracil, and leucovorin. Patients were eligible if they had progressive disease after either adjuvant (2 patients) or previous chemotherapy for metastatic disease (26 patients). Twenty-five patients (89.2%) had received previous anthracycline-based therapy. Predominant site of metastatic disease was visceral in 22 patients, bone in 2 patients, soft tissue in 4 patients, and the majority of patients (89.2%) had two or more sites of disease. The regimen was administered according to the following schedule: Mitoxantrone 9–12 mg/m2 i.v. on day 1; L-Leucovorin 150 mg i.v. over 1 hour before 5-Fluorouracil 350 mg/m2 i.v. push days, 1, 2 and 3. Courses were repeated every 21 days. Twenty-six patients were evaluable for response. We observed 2 complete responses, 5 partial responses with a median duration of 38 weeks (range 23–68). The objective response rate was 27% (95% C.I., 10% to 44%). Myelo-suppression was the most frequent toxicity, but it was mild in the majority of patients. Nine episodes of fever and neutropenia occurred in six patients but none of these episodes was fatal. No clinical evidence of cardiotoxicity was observed.At a median follow-up of 78 weeks, the median time to progression was 20.5 weeks and the median overall survival was 48 weeks.We conclude that this regimen is well tolerated and in our experience the objective response rate is similar to other salvage chemotherapy regimens.