Maria Cristina Santona

Medroxyprogesterone acetate reduces the in vitro production of cytokines and serotonin involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of cancer patients.

Medroxyprogesterone acetate (MPA) is widely used in oncology both in the treatment of hormone-related cancers and as supportive therapy in anorexia/cachexia syndrome (ACS), but conclusive data are not yet available to explain its anticachectic effect. ACS is characterised by weight loss, changes in metabolism, reduction of appetite, nausea and vomiting. Several cytokines, mainly interleukin (IL)-1, IL-2, IL-6 and tumour necrosis factor alpha (TNF alpha), are involved in the pathogenesis of ACS. Additionally, nausea and vomiting can be mediated by factors inducing serotonin (5-HT) production and/or release by pleiotropic cells including activated T lymphocytes. In the present study, we report the effect of MPA on peripheral blood mononuclear cells (PBMC) from 10 cancer patients in advanced stage of disease (6 head and neck, 2 colon, 1 lung and 1 ovary). The proliferative response of PBMC to PHA, anti-CD3 monoclonal antibody (MAb) or recombinant IL-2 (rIL-2), the production of IL-1 beta, IL-2, IL-6, TNF alpha and 5-HT by PHA-stimulated PBMC and the expression of lymphocyte membrane-bound IL-2 receptor (IL-2R) subunities (CD25 and CD122) were studied. The addition of MPA significantly reduced the PBMC proliferative response to PHA and anti-CD3 MAb but not to rIL-2. MPA 0.2 microgram/ml was also capable of reducing the levels of IL-1 beta, IL-6, TNF alpha and 5-HT produced in culture by PHA-stimulated PBMC, whereas it did not induce any change in the percentage of PBMC expressing either CD25 or CD122 or both molecules after stimulation with PHA or anti-CD3 mAb.

Comparison of granisetron, ondansetron, and tropisetron in the prophylaxis of acute nausea and vomiting induced by cisplatin for the treatment of head and neck cancer: a randomized controlled trial

BACKGROUND A single-institution, prospective, randomized, open controlled trial was carried out on head and neck cancer patients to compare granisetron (GRA), ondansetron (OND), and tropisetron (TRO) in the prevention of cisplatin-induced acute nausea and vomiting. All patients were chemotherapy-naive and treated with cisplatin on Day 1 (80 to 100 mg/m2). METHODS One hundred seventeen patients were treated for a total of 463 cycles of cisplatin-based chemotherapy and randomized to receive 24 mg of OND intravenously (i.v.), 3 mg of GRA i.v., or 5 mg of TRO i.v. for the control of acute nausea and emesis. RESULTS In the GRA group, complete response (CR) was obtained in 119 of 165 cycles (72.1%), major response (MR) in 32 cycles (19.4%), minor response (MiR) in 5 cycles (3%), and a failure (F) in 9 cycles (5.5%). In the OND group, CR was obtained in 110 of 150 cycles (73.3%), MR in 31 cycles (20.7%), MiR in 2 cycles (1.3%), and F in 7 cycles (4.7%). In the TRO group, CR was obtained in 100 of 148 cycles (67.6%), MR in 26 cycles (17.6%), MiR in 15 cycles (10.1%), and F in 7 cycles (4.7%). Major efficacy (CR + MR) was obtained in 151 of 165 cycles (91.5%) for GRA, in 141 of 150 cycles (94.0%) for OND, and in 126 of 148 cycles (85.2%) for TRO. The difference in major efficacy between OND and TRO was statistically significant. When comparing MiR, both GRA and OND were more effective than TRO. No other significant differences were observed among the three antiemetic agents. CONCLUSIONS Although our results were achieved in an open trial, they show that GRA and OND are equally effective antiemetic agents in the prevention of cisplatin induced acute nausea and vomiting. TRO provides almost the same protection but is not as effective as OND for major efficacy. All three antiemetics can be administered safely to patients undergoing chemotherapy with cisplatin at doses of 80 mg/m2 or more.

Neo-adjuvant chemotherapy ± immunotherapy with s.c. IL 2 in advanced squamous cell carcinoma of the head and neck: A pilot study

We carried out a pilot nonrandomized phase II study to compare the neo-adjuvant chemotherapic regimen with cisplatin, 5-FU and vinorelbine with the same combination plus s.c. IL 2 in advanced head and neck squamous cell carcinoma (HNSCC). The primary goals of the trial were to evaluate the feasibility and response rates of the two regimens. The study design consisted of a patients assignment to either of the two following arms: Arm A: Cisplatin 80 mg/m2 i.v. on day 1; 5-FU 600 mg/m2 i.v. on days 2–5; and vinorelbine 20 mg/m2 i.v. on days 2 and 8, Arm B: the same chemotherapic regimen plus recombinant IL 2 (Proleukin, Eurocetus) 9 MIU s.c. daily from day 9 to 13 and from day 16 to 20 for every cycle. From March 1993 to November 1993 twenty three patients with Stage III–IV HNSCC were enrolled in the study. Patients could be evaluated for response to treatment if they had received at least 2 complete cycles of therapy. The overall response rate (ORR) was 63% in Arm A and 100% in Arm B. The differences for ORR and CR rates were statistically significant in favor of Arm B. The analysis for each of the three drugs included in the chemotherapy schedule shows that both the actually received average dose-intensity and the actually delivered average cumulative doses/patient were higher for Arm B (chemo- plus IL 2 therapy) (approximately 80% of programmed dose-intensity) than for Arm A (approximately 70% of programmed dose-intensity). Both the actually received average dose-intensity and the actually delivered average cumulative doses/patient for IL 2 were more than 80%. In both arms the most frequent side effects were myelosuppression, phlebitis and electrolyte disturbances. There were 2 toxic deaths, 1 in Arm A and 1 in Arm B, both for hematologic toxicity. Our “pilot” study suggests that the combination of cisplatin, 5-FU, vinorelbine plus IL 2 is a highly active, but rather toxic, neo-adjuvant treatment in advanced HNSCC with very high ORR and CR rates.

Neo-adjuvant (primary) organ-preserving chemotherapy in the management of locally advanced laryngeal carcinoma

We designed an open, non-randomized, phase II clinical study to assess as the first endpoint the feasibility of sparing surgery and of preserving organ/function by using neoadjuvant chemotherapy (NAC) laryngeal cancer patients, and, as the second endpoint, the clinical response to this treatment approach and its duration. 32 patients with primary laryngeal cancer (stage III-IV) were enrolled in the study and were assigned to either the classical Al-Sarrafs regimen (20 patients) or to a regimen consisting of cisplatin 80 mg/m(2) i.v. on day 1, 5-FU 600 mg/m(2) on days 2-5 and vinorelbine 20 mg/m(2) on days 2 and 8 (12 patients). The patients were divided into 2 groups: A) those requiring total laryngectomy (TL) and B) those not requiring TL, i.e. patients eligible for conservative for conservative surgery. The 32 patients were all evaluable for response to NAC and 31 were evaluable for The complete remission rate was 50% (16/32) and the partial remission rate was 46.9% (15/32) with an overall response rate of 96.9%. The median follow-up duration was 20.2 months. Overall, 23 patients required TL (group A) and 8 patients a conservative laryngectomy (group B). 7/23 (30.5%) patients of group A did not undergo surgery (score 4) and 6/23 (26%) achieved a partial larynx preservation (3/23 score 3, 1/23 score 2, 2/23 score 1), while 10/23 (43.5%) received the previously planned TL (score 0). 5/8 (62.5%) patients of group B did not undergo surgery, whereas 3/8 (37.5%) received the previously planned surgery (score 0). Therefore, 12/31 patients (38.7%) completely avoided surgery and 6/31 (19.4%) achieved a reduction in the extent of planned surgical resection, that is 18/31 patients (58.1%) achieved a reduction in the extent of previously planned surgery attributable to NAG. Moreover, 3/31 patients underwent the previously planned conservative surgery consisting of H-SGL/HG. Altogether 21/31 (67.7%) patients preserved function. The most relevant contributions offered by our study are represented by i) a scale aimed at measuring as precisely as possible the reduction of surgical resection made possible by NAC compared to surgery planned before NAC and ii) by an attempt to support the results with an assessment of patients treatment outcome. Although the scale provided by us is an arbitrary one, it must be emphasized that our goal was to address the issue of quality of life in cancer patients by a more precise quantification of organ/function preservation.