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We enrolled 19 cancer patients (11 females, 8 males) with thrombocytopenia after standard dose of chemotherapy to receive IL3 10 mg/kg/day s.c. until hematologic recovery. Therapeutic success was obtained in 69.6% of cycles; a major response in 39.3% and a minor response in 30.3% of cycles. We obtained the best results in case of platelet count <49,000/mm3. The main toxicity was a flu-like syndrome. In two cycles (6%) we registered allergic episodes with flushing and lipothymia. In the 47% of cycles evaluable for toxicity no side effect was registered.

We studied a consecutive series of 78 stage I cutaneous malignant melanoma in order to identify variables which might predict development of metastases. Anatomical site, sex, tumor thickness, Clark level, microscopic ulceration, growth phase, histologic type, cell type, and DNA ploidy were investigated. Lesions with tumor thickness 1.5 mm, Clark level IV-V, microscopic ulceration and DNA aneuploidy were at high risk for the development of metastases. This study showed the prognostic importance of DNA ploidy in stage I cutaneous malignant melanoma and the strong relationship between DNA ploidy and classic prognostic factors. This variable can be used in routine diagnosis for selecting a high-risk group of patients who may benefit from a more aggressive therapeutic approach.

We enrolled 11 consecutive pre-treated resistant advanced cancer patients to receive hydroxyurea (HU) (as modulator of MDR) 10 mg/kg/day (d) p.o. d 1-14 in association with DXR (d 15) alone or in combination with VDS (d 15) or VP16 (d 15-17) in presence, respectively, of soft tissue sarcoma, breast carcinoma, lung and gastric carcinoma. We obtained a stabilization of disease (NC) in 62.5% of patients, with a mean duration of 6 months. The mean survival was 12.2+ months for NC and 6 months for progressive disease (PD). No severe or unexpected adverse events were reported over 34 cycles administered; the most frequently recorded side effects were haematological and gastrointestinal toxicity. It seems that at the dosage we used, HU is poorly active in overcoming MDR; further studies with larger number of patients and different dosage are needed.

The role of chemotherapy in refractory metastatic breast cancer is still debated. We employed a schedule of cisplatin, mitomycin and vindesine in twenty-one anthracycline- or anthraquinone-pretreated breast cancer patients. The most relevant characteristics of our group were a good performance status (mean Karnofsky index 84) and a high percentage of bone disease (71%). Out of 20 evaluable patients, 4 (20%) achieved a partial response with a median duration of 3.7 months. Median survival was 12.5 months. Severe gastrointestinal toxicity was reported in 66% of patients and G3 alopecia was seen in 24%. Other side effects, including hematological, were negligible. On the basis of the low response rate and poor tolerability we do not reccommend this combination as salvage treatment in metastatic breast cancer. The use of cisplatin-based regimens in untreated patients waits further investigation.

We enrolled 118 chemonaive cancer patients (pts) to receive OND i.v. dl or GRA i.v. dl. Seventy of the 118 pts received moderately emetogenic (ME) chemotherapy (140 cycles), while 48 received highly emetogenic (HE) chemotherapy (93 cycles). Therapeutic success was obtained in 89% (OND) vs 94% (GRA) cycles of HE and in 96.8% (OND) vs 95.6% (GRA) cycles of ME. The main toxicities were headache (24%, OND; 23%, GRA); light-headedness (13%, OND; 18%, GRA); constipation (11%, OND; 6%, GRA). In conclusion, we think that OND and GRA are effective and the two drugs are equally active and toxic.

Treatment of advanced head and neck cancer is still a matter of controversy. Although current chemotherapy regimens are able to induce high response rates, they have not shown improved survival. We employed a combination of cisplatin (CDDP), 5-fluorouracil (5FU) and 1-folinic acid (1-FA) in a 6-hour infusion schedule easy to administer on an outpatient basis. 49 patients have been included to date. The treatment plan consists of 5-FU (375 mg/m(2)) plus 1-FA (100 mg/m(2)) in a 4-hour i.v. infusion followed by a 2-hour i.v. administration of CDDP (20 mg/m(2)). This therapy was repeated for five consecutive days and recycled every 3-4 weeks. Out of 46 evaluable patients there were 6 complete responses (CR) and 23 partial responses (PR) for an overall response rate of 63%. Overall survival was 10.2 months (mean). Untreated patients had a higher probability of response as well as patients with naso-oropharyngeal primary tumor. Toxicity was generally mild with leukopenia, anemia and vomiting being the most frequent side effects. In conclusion, this combination appears well tolerated and active in the palliation of advanced head and neck cancer. However we think that increasing dose intensity of standard regimens and experimental new therapeutic approaches are needed to improve the clinical outcome of this disease.

The antiproliferative effects of interferon-alpha (IFN-alpha) and of its combination with doxorubicin (DXR) were studied on three tumor cell lines, the mouse B16 melanoma and Friend erythroleukemia and the human K562 erythroleukemia, both as DXR-sensitive (B16, FLC, K562) and resistant (B16-DXR, FLC-DXR, K562-DXR) variants; the latter lines were endowed with typical multidrug resistance (MDR). Growth inhibition by IFN-alpha was greater in B16-DXR and FLC-DXR than in their chemosensitive counterparts and was superimposable in K562 and K562-DXR. On the other hand, the combination of IFN-alpha and DXR turned out to be merely additive in B16, B16-DXR, K562 and K562-DXR; it was synergistic in FLC and antagonistic in FLC-DXR. Our results and those of others seem to indicate that synergy between IFN-alpha and DXR may occur rarely in MDR cells.