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.

Molecular weight of chitosan influences antimicrobial activity in oil-in-water emulsions.

The objective of this study was to evaluate the antimicrobial efficiency of chitosans in oil-in-water emulsions. Model emulsions were prepared with 20% corn oil, 1.5% Tween 20, 1.5% Trypticase soy broth, 0.58% acetic acid, and chitosan polysaccharide or chitosan oligosaccharide in concentrations of 0, 0.1, 0.2, 0.5, and 0.7%. A control containing HCl was included to determine the role of acetic acid in the overall antibacterial activity. The pH of samples and controls was adjusted to 4.5. Emulsions were inoculated with Listeria monocytogenes (strains Scott A and 310) or Salmonella Typhimurium DT104 (strains 2486 and 2576) at a level of 10(7) CFU/ml. Inoculated emulsions were incubated at 10 and 25 degrees C for 4 days and analyzed for bacterial count every 24 h. Both tested Salmonella strains were more susceptible to acetic acid than Listeria. However, L. monocytogenes was more affected by chitosan than either Salmonella strain. During the storage at 25 degrees C, initial inoculum in the emulsions with 0.58% acetic acid and 0.1% chitosan polysaccharide was reduced to below the detection limits after 24, 48, 72, or 96 h for L. monocytogenes 310, Salmonella Typhimurium DT104 2576, Salmonella Typhimurium DT104 2486, or L. monocytogenes Scott A, respectively. Chitosan oligosaccharide was less effective against all tested bacteria and showed a concentration-dependent effect. The antimicrobial efficacy of chitosan was reduced at 10 degrees C, and reduction of microbial loads was delayed for approximately 24 h compared with 25 degrees C. Results suggest that addition of 0.1% chitosan polysaccharide would be sufficient to ensure the microbial safety of oil-in-water emulsions regardless of storage temperature.

Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer.

Synergism between anti-HER2 monoclonal antibody (trastuzumab) and paclitaxel has been shown in vitro and in vivo. In previous experiences, weekly administration of trastuzumab and paclitaxel has shown significant activity in metastatic breast cancer. In this phase II study, we evaluated the activity and the toxicity of this weekly regimen in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer. Between November 1999 and July 2001, 25 patients were treated with trastuzumab (4 mg kg(-1) i.v. loading dose followed by 2 mg kg(-1) i.v. week(-1)) and paclitaxel (60-90 mg m(-2) h(-1) i.v. infusion week(-1)). The treatment was planned to continue until disease progression or prohibitive toxicity; in patients with responsive or stable disease, after 6 months of therapy, the decision to stop paclitaxel while continuing weekly trastuzumab was left to the physicians' judgement. At the median follow-up of 19.6 months (range 9.2-38.1), all patients are evaluable for response and toxicity. We obtained four (16%) complete responses (CR), 10 (40%) partial responses (PR), four (16%) stable diseases and seven (28%) disease progressions. The response rate (CR+PR) was 56% (95% CI, 36.5-75.5%). The median duration of response was 10.4 months (range 4.1-24.2+). Median time to progression was 8.6 months (range 2.5-24.2+). The toxicity was mild; five patients experienced fever and chills during the first infusion of trastuzumab (20%); leukopenia grade 2 was recorded in one patient (4%). Two patients (8%) came off study for grade 3 cardiotoxicity (after 9 and 17 weeks of treatment, respectively): both had already received anthracyclines and taxanes. Onycholysis grade 2 was observed in five patients (20%). These results confirm that weekly administration of trastuzumab and paclitaxel is active in anthracycline- and taxane-pretreated metastatic breast cancer patients HER2-overexpressing. Since cardiac disfunctions grade 3 were observed (8%), we recommend that cardiac function should be monitored in these patients.

Results of a prospective study with high-dose etoposide, thiotepa and carboplatin and peripheral blood stem cell rescue for high-risk stage II-IIIA and selected stage IV breast cancer patients.

AIMS AND BACKGROUND: To investigate the safety and efficacy of a high-dose chemotherapy regimen with etoposide, carboplatin and thiotepa in high-risk stage II-IIIA breast cancer and in responsive metastatic patients. STUDY DESIGN: From April 1992 to December 1998, 24 patients with high-risk stage II-IIIA breast cancer (> or = 9 positive nodes) and 9 responsive metastatic patients were enrolled in the trial. After induction chemotherapy with an anthracycline-based regimen, peripheral blood stem cells were mobilized with cyclophosphamide (7 g/m2) and G-CSF (5-16 microg/kg/s.c./day). The high-dose chemotherapy regimen consisted of etoposide (1000 mg/m2), carboplatin (800 mg/m2) and thiotepa (500 mg/m2). At the end of the high-dose chemotherapy, all stage II-IIIA patients received radiotherapy to the breast or chest wall and draining nodes; stage IV patients were irradiated to sites of disease, if feasible. All ER+ and/or PgR+ patients were treated with hormone therapy. RESULTS: For stage II-IIIA high-risk patients, the median follow-up was 4.36 years (range, 1.93-6.94), and the Kaplan-Meier estimate at 5 years of disease-free survival and overall survival was 54.8 +/- 11% SE and 76.73 +/- 9.4% SE, respectively. For metastatic patients, the median follow-up was 4.93 years (range, 4.15-7.95), and the Kaplan-Meier estimate at 5 years of progression-free survival and overall survival was 22.2 +/- 13.9% SE and 76.2 +/- 14.8% SE, respectively. No treatment-related deaths were observed. CONCLUSIONS: Our results are comparable to those obtained in other high-dose chemotherapy trials but do not seem to be superior to conventional-dose therapy given to similar patients.

Long-term results in patients with advanced epithelial ovarian carcinoma treated with a combination of cisplatin, doxorubicin, and cyclophosphamide.

From 1984 to 1988, thirty-nine untreated patients with epithelial ovarian cancer received Cisplatin 50 mg/m2, Doxorubicin 50 mg/m2, and Cyclophosphamide 750 mg/m2 (CAP), at 3 weekly intervals. All patients had FIGO stage III or IV tumors except 2 patients with stage IIb and IIc, respectively. After initial surgery 23 patients had residual disease > 2 cm in diameter. Twenty-five patients (64%) were evaluable for response to chemotherapy. Objective responses were observed in 13 out of 25 patients (52%, 95% confidence intervals (CI), 32.42% to 71.58%), 6 patients had a cCR (24%) and 7 had a cPR (28%). Seventeen out of the 39 patients (44%) had a second-look laparotomy. A pCR was achieved in 5 out of 17 patients (29%); a pPR was obtained in 8 patients (47%). Median duration of survival was 41,5 months (range 2-107+); median duration of time to failure was 21 months (range 2-107+). Median disease-free survival was 86 months (range 3,5-107+). Eleven patients (28%) are alive and 9 patients (23%) are free of recurrence at median follow-up of 86 months. Only 4 of 11 long-term survivors had a pCR. In univariate analysis, histology, clinical response to chemotherapy, and the presence of ascites at the time of diagnosis, achieved a significant correlation with survival and time to failure (TTF); in addition, TTF was significantly affected by pathological response to induction chemotherapy. The only important predictors of disease-free survival (DFS) were tumor grade and stage of disease. In multivariate analysis, the presence of ascites was the only significant prognostic factor with respect to survival and TTF. Our study confirms the effectiveness of CAP in the treatment of epithelial ovarian cancer and the relatively poor long term prognosis.

[Recent improvements in antiemetic therapy]. / Ottimizzazione della terapia antiemetica.

In the past few years important progress in the prevention of chemotherapy-induced nausea and vomiting has been made mainly thanks to the introduction of the 5-HT3 receptor antagonists in clinical practice (ondansetron, granisetron, tropisetron). In the prevention of acute emesis induced by cisplatin, an intravenous combination of a 5-HT3 receptor antagonist plus single dose dexamethasone (20 mg) should be considered the treatment of choice. This is also the case in the prevention of acute emesis induced by moderately emetogenic chemotherapy (intravenous cyclophosphamide, doxorubicin, epirubicin, carboplatin, used alone or in combination), but high and repeated doses of dexamethasone should be used (8 mg intravenously plus 4 mg orally every 6 hours for four doses starting contemporarily to chemotherapy administration). Several-well conducted double-blind comparative studies among intravenously administered 5-HT3 receptor antagonists have been carried out. Almost all showed that they have identical antiemetic activity and tolerability. Therefore, the choice among 5-HT3 receptor antagonists should be based only on their acquisition cost in each country. In the prevention of delayed emesis (from day 2 to day 4) induced by cisplatin oral metoclopramide (0.5 mg/kg or 20 mg every 6 hours for four doses daily) and oral ondansetron (8 mg twice daily), both combined with dexamethasone, showed similar antiemetic efficacy. Metoclopramide plus dexamethasone should be considered the antiemetic regimen of choice due to its lower cost. Ondansetron plus dexamethasone is a valid alternative regimen that should be preferred in patients who not tolerate metoclopramide and in patients who suffer from acute vomiting. In the prevention of delayed emesis induced by moderately emetogenic chemotherapy oral dexamethasone or oral ondansetron showed a good antiemetic efficacy, but the results from a recently published study seem suggest the necessity to treat only patients who present acute vomiting or moderate-severe nausea. In fact, patients obtaining complete protection from vomiting and nausea (or at most mild acute nausea) have a very low incidence of delayed emesis.

Efecto del GnRH combinado con destete temporal y definitivo sobre el anestro posparto en vacas cebú en el trópico húmedo / Effect of combined GnRH, temporary and definitive weaning on postpartum anestrus in Zebu cows in the humid tropics

Este experimento se efectuó con la finalidad de buscar alternativas de solución al anestro posparto en vacas Bos indicus. Se utilizaron 38 vacas Cebú Gyr e Indobrasil, entre 90 y 120 días posparto, en anestro y con buena condición corporal. Los animales se asignaron aleatoriamente a cuatro grupos: 7 vacas (Grupo A) recibieron 20 mg de bucerelina (GnRH) por vía intramuscular (im) y fueron destetadas temporalmente por 72 horas; 12 vacas (Grupo B), sólo fueron destetadas temporalmente por 72 horas; a 9 vacas (Grupo C) se les aplicó 20 mg de GnRH vía im y fueron destetadas definitivamente, y 10 vacas (Grupo D), sólo recibieron 20 mg de GnRH vía im y continuaron amamantando. Las vacas se observaron 2 veces por día para detectar estros, durante 45 días postratamiento. La inseminación artificial (IA) se realizó 12 horas después de detectado el estro. Se calcularon el intervalo tratamiento-IA (T-IA), índice de no-retorno a estro y tasa de preñez. El porcentaje de animales que presentaron estros durante el periodo fue superior en el grupo C (7/9) (P< 0.01), en contraste con los grupos D (5/10), A (2/7) y B (2/12), entre los que no fue significativa la diferencia (P> 0.05). El T-IA fue significativamente menor (P< 0.01) en el grupo C (9 ñ 2 días), en contraste con los grupos D, B y A (29 ñ 2.9, 35 ñ 6 y 52 ñ 9 días, respectivamante); entre los cuales no hubo diferencias (P> 0.05). Los índices de no-retorno a estro fueron 88.9 por ciento, 100 por ciento, 66.6 por ciento y 70 por ciento para los grupos A, B, C y D, respectivamante (P> 0.05). Se obtuvieron 28.6 por ciento (2/7), 41.7 por ciento (5/12), 22.2 por ciento (2/9) y 10 por ciento (1/10) de vacas gestantes para los grupos A, B, C y D respectivamante. La fertilidad de los servicios de IA fue de 100 por ciento para los grupos A, B y D, con contraste con el 40 por ciento en el grupo C (P< 0.01). Se concluye que la combinación de GnRH y el destete definitivo de las crías, fue el tratamiento más eficaz para disminuir la duración del anestro posparto; sin embargo, no mejoró la fertilidad a la primera inseminación

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

From 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.

Ondansetron.

Ondansetron is the first selective antagonist of the 5-hydroxytryptamine receptors (type 3) marketed for the prevention of emesis induced by antineoplastic agents. Ondansetron has been shown to be more active and less toxic than high-dose metoclopramide in patients submitted to cisplatin chemotherapy. Furthermore, when dexamethasone was added to ondansetron, its antiemetic efficacy increased significantly. In the prevention of emesis induced by a high single dose of cisplatin or by repeated low doses, ondansetron combined with dexamethasone has been shown to be the more efficacious and less toxic antiemetic treatment. However, in the prevention of delayed emesis from cisplatin, its role is still to be defined. In patients submitted to moderately emetogenic chemotherapeutic agents, ondansetron has shown an efficacy superior or equal to standard doses of metoclopramide, but is less toxic. Moreover, when compared with dexamethasone, its antiemetic efficacy and tolerability is similar; in this group of patients ondansetron should be used only when steroids fail. Ondansetron toxicity is generally mild; in particular, it does not induce extrapyramidal reactions. The most frequent side-effects are headache and constipation.

Reliability and validity of a quality of life questionnaire in cancer patients.

Two studies were sequentially conducted to validate a new questionnaire which takes into consideration the most important variables which could influence quality of life evaluation. Particular attention was given to the methodology employed to collect data and to the patients' characteristics. In the first study 80 consecutive cancer patients were randomised to twice fill in one of four different types of questionnaire, each one characterised by a different polarisation of semantic and syntactic extreme values of the visual linear analogue (for instance, "very much" always on the right, regardless of the semantic value of the answer; positive semantic value always on the right, regardless of whether it was "very much" or "not at all"; and so on). The second study, conducted on 60 lung cancer patients, consisted in testing the reliability (by measuring the reproducibility in different ways) and the validity (by performing a factor analysis) of the type of questionnaire indicated by the first study as the most reliable. The internal coherence was also evaluated by measuring the effects of physical and psychological conditions on the responses.

Antiemetic activity of two different high doses and schedules of metoclopramide in dacarbazine-treated cancer patients.

The antiemetic activity of two different high doses and schedules of metoclopramide in dacarbazine-treated cancer patients was compared in a double-blind crossover study. Regimen A consisted of metoclopramide [2 mg/kg x 4 intravenously (i.v.)] plus methylprednisolone (250 mg x 2 i.v.) plus diphenhydramine (50 mg x 2 i.v.). Regimen B consisted of metoclopramide (3 mg/kg x 2 i.v.) plus dexamethasone (20 mg i.v.) and diphenhydramine (50 mg i.v.). Both treatments were administered for the first 2 days of 5-day dacarbazine chemotherapy. Thirty-two patients (13 men and 19 women) affected by melanoma and sarcoma were entered in the study. Complete protection against nausea and vomiting for the first 2 days of chemotherapy in both antiemetic regimens was not significantly different. Patient preference and tolerance of the two antiemetic treatments were similar. Regimen B, employing a lower dosage of metoclopramide and steroids and using a more simple schedule of administration should be the preferred treatment.

Intra and interobserver variability in cancer patients' performance status assessed according to Karnofsky and ECOG scales.

The Karnofsky (K) and ECOG (E) performance status (PS) scales are widely used to evaluate the functional status of cancer patients to determine their eligibility for clinical trials and their prognosis, but knowledge of inter and intraobserver variability of these scales is scarse. We therefore planned a prospective study on 209 consecutive cancer patients to evaluate this critical point. Two independent observers evaluated the KPS and EPS of each patient by interviewing them on the same day. After their interviews the patients were asked to fill in, again on the same day, a self-evaluation scale concerning their ability to perform the routine activities of daily life. The 209 patient self-evaluation scales were presented twice, randomly and blinded, to the two observers who had participated in the evaluation of PS as well as to one other observer who had not. The interobserver correlation for both scales was very high (K = 0.921 for KPS and K = 0.914 for EPS) as was the intraobserver correlation (for KPS: K = 0.993, K = 0.960, and K = 0.959 and, respectively, for EPS: K = 0.982, K = 0.970, and K = 0.920). On the basis of these results, it appears that evaluation of PS made by a clinical oncologist using K or E scales can be very reliable and is a guarantee of optimal selection of cancer patients for inclusion in clinical trials.

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.

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.

Assessment of nausea.

In 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 lorazepam in prevention of nausea and vomiting in cisplatin-treated male patients.

In a pilot study we evaluated the efficacy and tolerability of a four-drug antiemetic combination (metoclopramide, dexamethasone, diphenhydramine and lorazepam) in cancer patients submitted to cisplatin chemotherapy at doses greater than or equal to 50 mg/m2. Fifty male patients entered the study. Complete protection from vomiting and nausea was obtained in 41 patients (82%) (95% confidence limits 71 and 93%). Toxicity was slight except for moderate sedation in 10% of patients necessitating their hospitalization. Only one extrapyramidal reaction (akathisia) was observed. When these results were compared to our previous experience in male patients treated with a combination of metoclopramide, dexamethasone and diphenhydramine without lorazepam, used at the same doses and schedule, no clear benefit and higher toxicity was observed.

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

A 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.

Protection from nausea and vomiting in cisplatin-treated patients: high-dose metoclopramide combined with methylprednisolone versus metoclopramide combined with dexamethasone and diphenhydramine: a study of the Italian Oncology Group for Clinical Research.

Despite treatment, emesis remains a major problem with cisplatin (CDDP) chemotherapy. Reasons for variability in antiemetic response among patients and in subsequent cycles are largely unknown and toxicity is sometimes severe. We have, therefore, carried out a multicenter, double-blind randomized trial comparing a combination of high-dose metoclopramide (MTC) (1 mg/kg x 4) and methylprednisolone (P) (treatment A) with a shorter but higher single-dose schedule of metoclopramide (3 mg/kg x 2) combined with dexamethasone (DEX) and diphenhydramine (DIP) to prevent extrapyramidal reactions (treatment B). Three hundred sixty-seven consecutive patients treated with various chemotherapy combinations containing CDDP were studied. Complete protection from vomiting/nausea was, at first cycle, 72.5%/79.5% with treatment B and 55.8%/65.1% with treatment A, a statistically significant difference (P less than .002/P less than .005). In subsequent cycles, protection from emesis significantly decreased with no difference between the two treatments. Multifactorial analysis shows that women, younger patients, outpatients, and patients who experienced emesis in previous cycles were at higher risk of suffering nausea and/or vomiting. Both regimens were well tolerated, but patients treated with treatment B had significantly less extrapyramidal reactions (1.7%/6.1%, P = .053). Treatment B is preferred due to its greater efficacy and lower incidence of extrapyramidal reactions. Trials on antiemetic therapy should take into account the important variables able to influence the efficacy of treatment. There is still a need for improving prevention of emesis in CDDP-treated patients.