Metronomic chemotherapy (mCHT) in metastatic triple-negative breast cancer (TNBC) patients: results of the VICTOR-6 study.

PURPOSE: Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. METHODS: We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). RESULTS: Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9-7.2) and 12.1 months (95% CI: 9.6-16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0-18.4), 6.1 months (95% CI: 4.0-8.9) for CTX-based and 5.3 months (95% CI: 4.1-9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3-16.7 and CTX-based ones (95%CI: 8.7-52.8). Tumour response, PFS and OS decreased proportionally in later lines. CONCLUSION: This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.

Final results of the real-life observational VICTOR-6 study on metronomic chemotherapy in elderly metastatic breast cancer (MBC) patients.

Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients. Aim of this analysis is to provide insights into mCHT's activity in a real-life setting of elderly MBC patients. Data of patients ≥ 75 years old included in VICTOR-6 study were analyzed. VICTOR-6 is a multicentre, Italian, retrospective study, which collected data on mCHT in MBC patients treated between 2011 and 2016. A total of 112 patients were included. At the beginning of mCHT, median age was 81 years (75-98) and in 33% of the patients mCHT was the first line choice. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 27.9% and 79.3%, respectively. Median PFS ranged between 7.6 and 9.1 months, OS between 14.1 and 18.5 months. The most relevant toxicity was the hematological one (24.1%); severe toxicity (grade 3-4) ranged from 0.9% for skin toxicity up to 8% for hematologic one. This is a large study about mCHT in elderly MBC patients, providing insights to be further investigated in this subgroup of frail patients.

Metronomic chemotherapy for advanced breast cancer patients in the real world practice: Final results of the VICTOR-6 study.

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3-10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8-11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3-15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.

Raltitrexed plus levofolinic acid and bolus/continuous infusion 5-fluorouracil on a biweekly schedule for elderly patients with advanced colorectal carcinomas.

BACKGROUND: The aim of the study was to evaluate the safety and efficacy of the raltitrexed/5-fluorouracil/levofolinic acid combination regimen as first-line chemotherapy for elderly patients with advanced/metastatic colorectal cancer. PATIENTS AND METHODS: Previously untreated patients with metastatic colorectal cancer received raltitrexed 2 mg/m(2) i.v. plus levofolinic acid and 5-fluorouracil according to the De Gramont' schedule given every 2 weeks as first-line chemotherapy. Patients were re-evaluated after six cycles and chemotherapy was continued up to tolerance or disease progression. RESULTS: Seventy patients aged >/=65 years were accrued from 11 centers between September 2001 and July 2002. According to the intention-to-treat analysis, the overall response rate was 35% (95% CI 29.5% to 40.5%) including one complete response (1%) and 24 partial responses (34%). Twenty patients (31%) showed a stabilization of disease for a tumor growth control rate of 64% (95% CI 57% to 71%). The median overall survival was 12.5 months and the median time to disease progression was 6.5 months. No toxic deaths or allergic reaction were recorded. Grade 4 toxicities were non-existent. The main hematological toxicity was grade 3 neutropenia, which occurred in 9% of patients, and grade 3 anemia in only one case, while no case of graded 3 thrombocytopenia was observed. Grade 3 non-hematological toxicities were asthenia (11%), transient increase of transaminases (10%) and diarrhea (4%). CONCLUSIONS: The results of this study suggest that the raltitrexed/5-fluorouracil/levolofinic acid combination is an effective and well tolerated regimen for the treatment of elderly patients with advanced colorectal cancer. Its ease of administration and patient's tolerance warrant further investigation over 5-fluorouracil/folinic acid regimens.

Subcutaneous recombinant-human-erythropoietin prevents chemotherapy-related anemia in patients with advanced cancer.

Nineteen patients with advanced cancer were randomly allocated to receive: (i) rhEpo 150 UI/kg subcutanously three times/week starting 24 hours after the completion of cisplatin- or carboplatin-based chemotherapy; or (ii) normal saline. There were 17 patients with advanced head and neck carcinoma and 2 patients with small cell lung cancer. Patients were monitored for hemoglobin level, hematocrit, WBC, PLT and reticulocytes. Patients who received rhEpo overall showed a 7.2 +/- 6.3% mean increase in Hb level over their pretreatment values, while control patients had a 26.4 +/- 12% decrease. This difference was statistically significant (p<0.001). No patients in the rhEpo group required transfusion, while 4 patients in the control group received packed red cell transfusion. No significant side-effects attributable to rhEpo were recorded, but 1 patient showed a transitory increase in PLT count. In conclusion, subcutaneous rhEpo may be safely administered to patients with advanced cancer and effectively prevents cisplatin- or carboplatin-related anemia.

Elf regimen in advanced gastrointestinal malignancies - an analysis of its clinical effectiveness and toxicity.

A multi-institutional phase 11 study of the combination of levofolinic acid 100 mg/m2, VP16 120 mg/m2 and 5-fluorouracil 500 mg/m2 for 3 consecutive days was carried out on a series of 73 evaluable patients with low performance status affected by locally advanced and/or metastatic gastrointestinal carcinomas. Site of primary tumor were: stomach 26, large bowel 20, pancreas 16, gall-bladder 5, and liver 6. Among patients with gastric carcinoma, 2 patients (8%) had a complete response with a mean duration of 6.8+ months, and 9 (35%) had a partial response with a mean duration of 5.8+ months, for an overall response rate of 43%. Overall response rate was largely unsatisfactory in colorectal carcinoma (20%), pancreatic (12%), gall-bladder and liver carcinomas. The treatment was very well tolerated with no grade 4 toxicity over a total of 267 cycles administered. Grade 3 leukopenia was seen in 25% of cases, and grade 2 thrombocytopenia in 18%. Vomiting never exceeded grade 2. Thus, the ELF regimen is quite active in advanced gastric carcinoma, and may be recommended as palliative treatment of patients who cannot receive intensive chemotherapy. On the other hand, it cannot be considered active in colorectal, pancreatic, gall-bladder and liver carcinomas, and its use should be discouraged in these neoplasms.

Gemcitabine plus vinorelbine in stage IIIB or IV non-small cell lung cancer (NSCLC): a multicentre phase II clinical trial.

A phase II study in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) was carried out to evaluate the clinical activity and toxicity of the chemotherapeutic combination of gemcitabine+vinorelbine (GEM/VNR). Forty-five patients (40 male, 5 female) with a median age of 67 years (range 37-73) and a median ECOG performance status of 1 (range 0-2) were enrolled into the trial. Twenty patients had stage IIIB (two positive supraclavicular nodes and 20 cytologically positive pleural effusion), and 25 had stage IV NSCLC. GEM 1000 mg/m(2) diluted in 250 cc(3) of normal saline was administered iv on days 1, 8, and 15, while VNR was given 30 mg/m(2) on days 1 and 8 every 4 weeks. The median number of courses/patient was 4 (range 3-7). According to an intent-to-treat analysis 2 (4%) patients had a complete response and 16 (36%; 95% CL 22-52%) had a partial response for an overall response rate of 40% (95% CL 26-56%). Twelve (27%) patients had stable disease and 15 (33%) were considered as treatment failures. Median overall survival of the whole series was 8+ months with 33% of patients alive at 1 year. Toxicity was generally mild. WHO grade 3-4 neutropenia was recorded in 22% of cases, grade 1-3 liver toxicity in 6% of patients and neutropenia-unrelated fever in 9%. This multicentre phase II study suggests that the GEM/VNR combination regimen is an active and well tolerated regimen in patients with stage IIIB/IV NSCLC. Larger studies comparing cisplatin-based regimens to new schedules without cisplatin are warranted.

Etoposide, doxorubicin (Adriamycin) and cisplatin regimen in advanced gastric adenocarcinoma: experience with a lower dose schedule.

A phase II trial of etoposide (100 mg/m2) on days 4, 5, 6, doxorubicin (Adriamycin, 20 mg/m2) on days 1, 7, and cisplatin (30 mg/m2) on days 2, 8 (EAP) was carried out in order to reduce toxicity associated with a full-dose EAP regimen for advanced and/or metastatic gastric adenocarcinoma. Out of 21 evaluable patients, 2 (10%) had a complete response (CR), 7 (33%) had a partial response (PR), 4 (20%) showed no change and 8 progressed (38%). The mean duration of response (CR+PR) was 8.4+ months. Survival of the whole group was 7.5+ months. Treatment was quite well tolerated by most patients on an outpatient basis. Grade 3 vomiting and leukopenia were seen in 30% and 35% of cases respectively. One patient had grade 3 esophagitis, and 1 patient was hospitalized for severe grade 4 febrile leukopenia. Although the EAP regimen cannot be considered a standard therapy for gastric cancer, the EAP schedule employed in this study seems to be better tolerated than those reported by other authors, and can safely be given on an outpatient basis.

Cisplatin plus vp16 as salvage treatment for advanced breast-carcinoma resistant or recurrent after 1st line chemotherapy for metastatic disease.

Forty patients with chemotherapy refractory metastatic breast carcinoma were enrolled in a phase II study of cisplatin 80 mg/m2 on day 1 plus VP16 100 mg/m2 on days 1-3 every 28 days. The overall response rate was 32% (95% CL 17-47%), with 2 patients (5%) showing a CR with a mean duration of 11.3 months, and 11 patients (27%) a PR with a mean duration of 7.8+ months. Seven patients (17%) had stable disease, and 20 patients (50%) progressed despite chemotherapy. One complete response and 4 partial responses were obtained in patients previously untreated with antracyclines. The overall survival was 10.2+ months. The mean survival of responding patients (CR+PR) was 15.5+ months, while that of non responders (NC+PD) was 8.6+ months. A total of 188 cycles were administered (4.7 cycles/patient) and the most frequent toxicities were gastrointestinal and hematological side-effects. The most severe toxicities were intense vomiting and anemia. Grade 3 vomiting was seen in 11 patients (27%), and grade 1-2 anemia in 30% of cases. Severe grade 3 leukopenia was seen in only 12% of cases. Mild renal toxicity was recorded only in 2 cases, while alopecia was observed in almost all patients. In conclusion, although CDDP plus VP16 regimen, may be safely given on an outpatient basis, its routine use as salvage treatment for chemotherapy refractory metastatic breast carcinoma is not recommended. This regimen may, however, be employed as second line chemotherapy in selected cases.

Usefulness of oral medroxyprogesterone acetate in the management of cancer-related cachexia-anorexia syndrome.

A study on the activity and tolerability of high-dose medroxyprogesterone acetate in the treatment of ACS in neoplastic patients was carried out in a series of 103 patients with advanced cancer beyond cure with standard chemotherapeutic or radiotherapeutic treatments. The treatment plan was: medroxyprogesterone acetate (MAP) 1,000 mg/day as liquid suspension orally at a single dose, for at least one month. If there was no improvement in body weight, SSA, performance status therapy was interrupted. An increase in body weight greater than or equal to 5%, in SSA score greater than or equal to 2 points, in performance status and then in quality of life were recorded as positive MAP-related events. Therapy-related toxicity was evaluated according to the WHO criteria. A mean body weight increased from 63 kg recorded before therapy to 67 kg recorded after 30 days of MAP. This difference was statistically significant (p<0.001). SSA increased from baseline value of 2.4 to 4.7, and mean performance status from 58.4 to 65. Again, these difference were highly significant (p<0.005 and p<0.001 respectively). The improvement in both mean body weight and SSA were statistically significant independent of performance status. Data presented in the present study confirm the clinical effectiveness of oral medroxy-progesterone acetate in the management of anorexia-cachexia syndrome in patients with advanced cancer resistant to systemic chemotherapy.

The in vitro effect of recombinant erythropoietin on cisdiamminodichloroplatinum-induced inhibition of murine erythroid stem cells.

An in vitro study was carried out to evaluate the possible protective effect of recombinant human erythropoietin (rhEpo) on cisplatin (CDDP)-induced inhibition of erythroid colony growth. CDDP at the dose of 0.4 mg/ml caused a 72-75% inhibition of erythroid stem cell growth in plasma clots. In the short-term assay rhEpo was not able to protect normal murine erythroid stem cells from the inhibitory effect of CDDP at any of the tested concentrations. In long-term bone marrow cultures, although the kinetics of cellular populations in suspensions and of erythroid stem cells were similar in both controls and CDDP-treated cultures, both cellularity and erythroid stem cells levels were much lower in CDDP-treated flasks than in control ones regardless of the addition of rhEpo. These results indicate that rhEpo is not able to prevent of ameliorate erythroid stem cell inhibition due to a possible toxic effect of CDDP, at least in vitro.

A prospective randomized trial of thymopentin versus granulocyte--colony stimulating factor with or without thymopentin in the prevention of febrile episodes in cancer patients undergoing highly cytotoxic chemotherapy.

One hundred patients with advanced carcinoma undergoing highly cytotoxic chemotherapy were enrolled in a prospective randomized trial comparing subcutaneous G-CSF, thymopentin, a combination of the two, and placebo as preventive treatment of febrile leukopenia. Data from this study show that G-CSF was very active in reducing the incidence of chemotherapy-related fever and leukopenia as compared to placebo (22% versus 64%). This difference was statistically highly significant (P < 0.001). Thymopentin was associated with a reduction in febrile episodes as compared to placebo (52% versus 64%), but this difference did not reach statistical significance. Moreover, the addition of thymopentin to G-CSF did not result in a statistically significant improvement of results obtained with G-CSF alone. Similar results were achieved for fungal infections. Tolerance to thymopentin was excellent, while less than 9% of patients on G-CSF treatment complained of mild nausea and generalized bone pain.

Levo folinic acid and 5-fluorouracil plus high dose epidoxorubicin as first line treatment for metastatic breast carcinoma.

Twenty-two women affected by metastatic breast carcinoma have been treated with a combination of levo folinic acid 100 mg/m2 plus 5-fluorouracil 450 mg/m2 i.v. on day 1-2, and epidoxorubicin 75-90 mg/m2 on day 2. This treatment cycle was repeated every 21-28 days. No patients had previously received chemotherapy for metastatic disease. Fourteen patients (64%) showed a major objective response with 3 complete (14%) and 11 partial responses (50%). Three patients showed a stabilization of disease and 5 (23%) progressed. All patients received ondansetron as antiemetic treatment which led to complete protection from vomiting in 68% of cases. Grade 1-2 diarrhea was recorded in 27% of the patients. Ten patients received recombinant human granulocyte-colony stimulating factor (rhG-CSF) as leukopenia-preventive treatment. In this group of patients the interval between chemotherapeutic cycles was shorter than in the group of 12 patients who did not receive rhG-CSF.

Vinorelbine plus cisplatinum for the treatment of stage IIIB and IV non small cell lung carcinoma.

Thirty consecutive patients with stage IIIB-IV non small cell lung cancer were treated with a combination of cisplatin 80 mg/m2 on day 1 plus vinorelbine 25-30 mg/m2 on days 1, 8. This cycle was repeated every 3 weeks. The overall response rate was 46%, with 1 patient showing a complete response and 13 patients (43%) a partial response with a mean duration of 8.4+ months. Six patients had a stabilization and 10 progressed. The main toxicities were represented by myelosuppression and nausea/vomiting. Grade 3 leukopenia was seen in 33% of cases, grade 2 thrombocytopenia in 12%, and phlebitis in the injection vein in 16%. Mild constipation was also recorded. The combination of cisplatin plus vinorelbine is quite effective in advanced non small cell carcinoma of the lung, and may be safely given on an outpatient basis.

Treatment of stage III-IV non-small-cell lung carcinoma with vinorelbine in combination with ifosfamide plus MESNA: a study by the Southern Italy Oncology Group (GOIM).

Thirty-five patients affected by stage III-IV non-small-cell lung carcinomas were treated with ifosfamide 3 gr/m2 plus MESNA as uroprotector on day 1 and vinorelbine 25 mg/m2 i.v. bolus on day 1 and 8. This cycle was repeated every 21 days. Over a total of 35 evaluable patients, the overall response rate was 34% (95% CL 18-54%). One patient experienced a complete response with a duration of 7.2+ months, and 11 patients a partial response with a mean duration of 5.9+ months. Seven patients had no change and 16 improved. The overall survival was 7.6+ months. Over a total of 145 cycles, the most frequent toxicity was myelosuppression, but grade 3 leukopenia and grade 2 thrombocytopenia were seen only in 14% and 9% of cases, respectively. Only one patient suffered grade 4 leukopenia. Gastrointestinal toxicity was minimal; only five patients (14%) complained of grade 3 vomiting. This combination regimen can be safely given on an outpatient regimen, but it is relatively active in advanced non-small-cell lung cancer. However, it should be noted that >50% of the patients in this series had a performance status of <80 and >50% were older than 65 years.

Weekly levofolinic acid and 5-fluorouracil plus hydroxyurea in metastatic gastrointestinal adenocarcinomas.

There were 42 patients with advanced gastrointestinal carcinomas (GA) enrolled in the study. In the Phase I part of the study we identified the MTD of 5-fluorouracil (5FU) in combination with levofolinic acid 100 mg/m2 per week intravenously plus hydroxyurea 1 g/m2 per week given by mouth in 3 refracted doses starting 6 hours after 5FU was administered. This treatment was given weekly for 6 consecutive weeks followed by a 15-day rest period. We were not able to increase 5FU weekly dosage above 700 mg/m2 due to the occurrence of grade 3-4 gastrointestinal toxicity. Thus 5FU was employed at 600 mg/m2 per week for the Phase II part of the study. Among 20 evaluable patients with measurable metastatic colorectal cancer, 1 patient had CR of 6.0+ months and 7 patients had PR with a mean duration of 6.2+ months, for an overall response rate of 40%. Four patients (20%) showed stable disease, and 8 patients progressed. The mean survival of the whole group was 5+ months (range: 3.0-12.8). This treatment was very well tolerated by most patients, with grade 3 diarrhea in 10% of cases and grade 3 vomiting in 20% of patients. Hydroxyurea (HU), employed at this dosage, seems not to increase 5FU/FA-related toxicity. This regimen is quite active in the management of advanced colorectal carcinoma, and may be safely given on an out-patient basis. A Phase III randomized trial may be established if HU improves results achievable with the 5FU-FA combination.

Vinorelbine plus cisplatin in recurrent or previously untreated unresectable squamous cell carcinoma of the head and neck.

Despite considerable progress achieved in the management of head and neck carcinomas (HNC) in the last decade, the prognosis of patients with advanced squamous cell HNC is still dismal. On the basis of the reported good activity of a new vinca alkaloid derivative, i.e., vinorelbine (VNR), we tested the combination of cisplatin and VNR in a series of patients with recurrent or previously untreated unresectable squamous cell HNC. Thirty-five patients with recurrent or previously untreated unresectable squamous cell HNC were treated with a combination of cisplatin 80 mg/m2 on day 1, plus vinorelbine 25 mg/m2 i.v. push on days 1 and 8. This cycle was repeated every 3 weeks. Analysis of response rates was carried out separately for previously untreated patients, and those with recurrent disease after surgery and/or radiotherapy. In the group of 20 patients with recurrent disease the overall response rate was 55% (95% CL 44-66%), with 3 patients (15%) showing a complete response with a mean duration of 6.2+ months and 8 patients showing a partial response with a mean duration of 8.6+ months. In the group of patients with previously untreated unresectable disease, 13 patients (87%, 95% CL 78-96%) had a major objective response with a complete response rate of 27%. This regimen was quite well tolerated, with meyelosuppression and vomiting being the most frequent toxicities. The occurrence of an acute pain syndrome following vinorelbine administration in 4 patients is noteworthy. In conclusion, this combination is active in advanced squamous cell head and neck carcinoma. However, although it may be recommended in recurrent carcinoma, the complete response rate achieved in previously untreated patients is lower than that reported with other more intensive regimens.

A prospective evaluation of the activity of human granulocyte-colony stimulating factor on the prevention of chemotherapy-related neutropenia in patients with advanced carcinoma.

After informed consent, 86 patients with advanced cancer undergoing potentially myelosuppressive cytotoxic chemotherapy were randomized to receive placebo or subcutaneous granulocyte-colony stimulating factor (G-CSF) 5 micrograms/Kg/day in order to prevent severe neutropenia and its related morbidity. The incidence of neutropenia (absolute neutrophil count < 1,000/mm3) was significantly reduced in patients receiving G-CSF than in controls (18% versus 42%; P < 0.05). The duration of neutropenia was also shortened by the administration of G-CSF (4.8 versus 8.2 days; P < 0.05). Therapy with G-CSF has also a positive impact on the dose-intensity of employed regimens. Patients treated with G-CSF showed oral fungal disease in 9% of cases, while control patients had a 21% incidence (NS). Patients treated with G-CSF received 91% of the programmed dose-intensity as compared to 71% of control patients (P < 0.05). These data strengthen the clinical usefulness of G-CSF in the prevention of chemotherapy-related neutropenia, infections, and reduction in dose-intensity. Further studies are required to establish if the increase in dose-intensity allowed by G-CSF treatment may positively influence the outcome of cancer patients.

Combination chemotherapy of 5-fluorouracil, epidoxorubicin and mitomycin C in the palliative treatment of locally advanced and/or metastatic adenocarcinoma of the stomach.

Thirty-seven consecutive patients with advanced and/or metastatic gastric adenocarcinoma received a combination of 5-fluorouracil 600 mg/m2 on days 1, 8, 29, 36; epidoxorubicin 75 mg/m2 i.v. on days 1, 29; mitomycin C 10 mg/m2 i.v. on day 1. This cycle was repeated every 8 weeks. Out of a total of 34 evaluable patients, 2 (5.8%) had a complete response and 7 (20.6%) had a partial response with an overall median duration of 40 weeks (range 20-128). The median survival of responding patients was not reached after a mean follow-up of 76 weeks, while that of patients with no change and progressive disease was reached at 36 and 13 weeks respectively. Treatment was generally well tolerated with hematological and gastrointestinal toxicities being the major side-effects. Despite the use of epidoxorubicin 75 mg/m2, the 26.4% (95% confidence limits 16-36%) objective response rate is not satisfactory. Evaluation of more aggressive protocols is strongly recommended within the limits of controlled trials.

The in vivo effects of recombinant human erythropoietin on cisdiamminodichloroplatinum-induced anemia in golden Syrian hamsters.

Recombinant human erythropoietin given subcutaneously is able to accelerate hematopoietic recovery in hamsters affected by cisplatin-induced anemia, increasing hemoglobin and hematocrit levels. The increase in hemoglobin and hematocrit levels. The increase in hemoglobin and hematocrit levels is not accompanied by an increase of platelet or granulocyte counts in the peripheral blood. However, an increase in the marrow concentration of burst and colony forming units--erythroid (BFU-E, CFU-E) is observed after recombinant human erythropoietin treatment. This increase in the concentration of marrow erythroid progenitors was accompanied by an increase in the percentage of these stem cells in DNA synthesis as assessed by exposure to ARA-Cyt. Recombinant human erythropoietin seems highly effective in ameliorating and/or preventing cisplatin-induced anemia in experimental animals.