Major concerns about radioimmunotherapy (RIT) administration early in the course of follicular lymphoma (FL) are long-term toxicity and the theoretical impairment of hematopoietic stem cell (HSC) harvest, but few data are available about mobilization rates after RIT. This study evaluates the impact of prior therapy with RIT (yttrium-90 ibritumomab tiuxetan) and different chemotherapy regimens in all FL patients (N = 103) attempting HSC mobilization at our institution over the last 7 years. Sixty-nine patients received R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone) or CHOP-like regimens, 21 patients received R-FM (rituximab-fludarabine-mitoxantrone), and 13 patients received RIT before HSC mobilization. Median CD34+ cell yield at first mobilization was 7.2 × 106/kg in the R-CHOP group versus 4.3 in the R-FM group versus 1.7 in the RIT group (P = .02 R-CHOP versus R-FM; P < .0001 R-CHOP versus RIT; P < .02 R-FM versus RIT). Although 8 of 13 patients initially failed to collect enough HSC after RIT, a second and/or salvage harvest was successfully performed in 7 patients, with 10 of 13 patients (77%) finally undergoing autologous stem cell transplantation (ASCT). No differences in engraftment kinetics were observed between the three groups (R-CHOP versus R-FM versus RIT). Although mobilization was significantly impaired in patients previously treated with RIT, a salvage HSC harvest and ASCT after RIT were safe and feasible in most patients.

This phase 2 estimation study evaluated docetaxel/cisplatin with/without panitumumab, an anti–epidermal growth factor receptor monoclonal antibody, as first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).Randomized patients received docetaxel/cisplatin (75 mg/m2 each) with/without panitumumab (9 mg/kg) in 21-day cycles. Patients randomized to panitumumab + chemotherapy could continue panitumumab monotherapy after completing six chemotherapy cycles without progression; patients randomized to chemotherapy alone could receive second-line panitumumab after progression. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints included overall survival (OS), overall response rate (ORR), time to response (TTR), duration of response (DOR), and safety. A protocol amendment limited enrollment to patients <70 years owing to excess toxicity in older patients and added mandatory pegfilgrastim/filgrastim support. Outcomes were also analyzed by human papillomavirus status.103 of the 113 enrolled patients were evaluable and randomized to receive ⩾1 dose of first-line treatment. Median PFS for panitumumab + chemotherapy was 6.9 (95% CI = 4.7–8.3) months versus 5.5 (95% CI = 4.1–6.8) months for chemotherapy alone (hazard ratio [HR] = 0.629; 95% CI = 0.395–1.002; P = 0.048). ORR for panitumumab + chemotherapy was 44% (95% CI = 31–58%) versus 37% (95% CI = 24–51%) for chemotherapy alone (odds ratio [OR] = 1.37; 95% CI = 0.57–3.33). Median OS for panitumumab + chemotherapy was 12.9 (95% CI = 9.4–18.5) months versus 13.8 (95% CI = 11.8–22.9) months for chemotherapy alone (HR = 1.103; 95% CI = 0.709–1.717). Median TTR for panitumumab + chemotherapy treatment was 6.9 weeks versus 11.0 weeks for chemotherapy alone. Median DOR was 8.0 (95% CI = 5.7–11.1) months with panitumumab + chemotherapy versus 5.1 (95% CI = 4.4–7.2) months with chemotherapy alone. Grade 3/4 adverse event incidence was 73% with panitumumab + chemotherapy versus 56% with chemotherapy alone. 41% and 55% of patients in the panitumumab + chemotherapy and chemotherapy-alone arms, respectively, received panitumumab monotherapy.The addition of panitumumab to docetaxel/cisplatin may improve PFS in recurrent/metastatic SCCHN and has the potential to improve outcomes in these fully, or mostly, active patients.

immunostimulating properties, plus 5FU, was the first adjuvant regimen to demonstrate a decrease in recurrence rate and increases in disease free and overall survival in patients with stage III colon cancer. These beneficial results, reported in a randomized, controlled study, have been updated at 7 years and demonstrate the effectiveness of the regimen in stage III colon cancer. A total of 929 patients with stage III colon cancer were randomized to receive either surgery alone versus levamisole alone, or 5Fu and levamisole in combination. The 5Fu and levamisole combination reduced the relapse rate by 41% and the overall cancer mortality by 33% Levamisole alone was not significantly different from the surgery alone control crown.

AIM The incidence of Pneumonocystis carinii pneumonia (PCP) is increasing in patients with cancer. The possible routes of transmission in this population, as well as the epidemiological data of PCP, are not very well understood. The collection and analysis of data concerning the predisposing factors for PCP will elucidate this subject. PATIENTS AND METHODS We studied 26 patients suffering from cancer who developed PCP during the five-year period 1997--2002. RESULTS Twenty-one patients had a solid tumor diagnosis while the remaining five had a lymphoma. All of them received intensive combination chemotherapy, while eight of them also received high-dose therapy and bone marrow transplantation. Nineteen of our patients had long hospitalization before the onset of PCP. All of them had received corticosteroids for various reasons. Among them, many patients had been exposed to radiotherapy and, in particular, in fields which encompass the major thoracic duct. Eighteen patients survived after the initiation of appropriate treatment, while eight others succumbed. CONCLUSION In this series, protracted deep lymphopenia, long hospitalization, radiotherapy and intensive chemotherapy were considered serious risk factors for developing PCP.

Purpose. To assess the antitumor efficacy and safety of a combination of vinorelbine (VNR) and cisplatin in patients with metastatic breast cancer previously treated with anthracyclines and docetaxel. Patients and Methods. Thirty-six patients with assessable metastatic breast cancer previously treated with anthracyclines and docetaxel (adjuvant n = 1, palliative n = 20, both n = 15) were studied. Cisplatin was given at 75 mg/m(2) on day I followed by 25 mg/m(2) VNR on days 1 + 8 in a 5-minute IV infusion. Courses were repeated every 3 weeks. Treatment was continued until disease progression, excess toxicity, or patient refusal. Patients were classified according to their response to anthracyclines according to criteria published previously: 1) Anthracycline and/or docetaxel resistant were patients who progressed during treatment with anthracyclines and docetaxel or within 4 months after cessation of treatment (metastatic). In addition, adjuvant patients who progressed within 6 months after completion of chemotherapy belong to this group. 2) Anthracycline and/or docetaxel relapsed were either metastatic patients who responded initially and then progressed after 4 months of completing an anthracycline- and docetaxel-based chemotherapy or patients who progressed after 6 months from completion of anthracycline/docetaxel-based adjuvant chemotherapy. Results. Two patients (5.6%) achieved a complete response (CR) and 15 patients (41.6%) achieved a partial response (PR), for an overall response rate (OR) of 47.2% (95% confidence interval, 31 -63). Of 18 patients relapsed to anthracycline/docetaxel, 2 had a CR (11%) and 8 a PR (44.4%), giving an objective response of 55.5%. Stable disease (SD) was observed in one patient (5.5%); seven patients had progressive disease (PD) (39%). Among the 18 resistant patients, 7 PRs (39%) were observed (p = 0.5), one patient (5.5%) had stable disease, 10 patients (55.5%) progressed. The median time to progression (TTP) was 16 weeks and median overall survival 36 weeks. Relapsed patients had a longer TTP than resistant patients (24 vs. 8 weeks, p = 0.05) but similar survival (48 vs. 24 weeks, p = 0. 173). All patients were assessed for toxicity. The main toxicity was neutropenia grade 3 and 4 in 47% of patients. Febrile neutropenia requiring hospitalization was absent. There were no treatment-related deaths. Thrombocytopenia grade 3 and 4 occurred in four patients (11%). Phlebitis, orthostatic hypotension, and asthenia, all reversible, were observed in 3% of patients, respectively. Conclusion. This cisplatin/VNR regimen is well tolerated and active in patients who failed anthracyclines and docetaxel treatment. The response rate, TTP, and survival data are high and indicate that cisplatin/VNR may have a place as salvage treatment in this group of patients. If these results can be verified in multi-institutional trials, this combination of drugs would merit investigation as part of a first-line therapy in breast cancer.

PURPOSE:To evaluate the efficacy and tolerability of a combination of vinorelbine (VNR) and docetaxel (DOC) as first-line chemotherapy in patients with metastatic breast cancer.PATIENTS AND METHODS:The study group comprised 40 women with untreated metastatic breast cancer with visceral (85%) and bone (70%) metastases. Of the 40 patients, 24 (60%) had previously received adjuvant chemotherapy, which had included anthracyclines in 12 patients (30%). Treatment consisted of VNR 25 mg/m(2) on days 1 and 5, and DOC 75 mg/m(2) on day 1 every 3 weeks. Depending on the neutrophil nadir (grade 3 or 4 neutropenia by WHO criteria) recombinant human granulocyte colony-stimulating factor (G-CSF) 5 micro g/kg on days 2-4 and 6-13 was given for all subsequent treatment cycles.RESULTS:The overall response rate (ORR) was 40% (95% confidence interval, CI 15-65). Six patients (15%) achieved a complete response (CR) and ten patients (25%) achieved a partial response (PR). Stable disease (SD) was observed in six patients (15%), and 18 patients (45%) had progressive disease (PD). The median duration of response was 8 months and the median predictive time to progression (TTP) was 6 months. The main toxicity was neutropenia grade 3 and 4 in 28 patients (70%). Febrile neutropenia requiring hospitalization occurred in 12 patients (30%). Grade 3 or 4 anemia was seen in two patients (5%) and grade 3 or 4 thrombocytopenia was seen in one patient (2.5%). Severe nonhematologic toxicity, except alopecia, was uncommon and included stomatitis in two patients (5%), vomiting in two (5%) and diarrhea in one (2.5%). There were no treatment-related deaths.CONCLUSIONS:The combination of VNR and DOC at the doses used in this study showed moderate activity as first-line chemotherapy in metastatic breast cancer. Neutropenia was considerable despite G-CSF administration.

Twenty-four patients previously treated with platinum containing regimens with stage IIIB-IV non-small-cell lung cancer (NSCLC) participated in the study. Sequential cohorts of patients were treated with 60 and 90 mg/m(2) of Paclitaxel per week. Paclitaxel was administered weekly over 1 h infusion for 6 consecutive weeks followed by 2 weeks without treatment (8-week cycle). A total of 252 treatments were administered to the 24 patients. In 29 (12%) of 252 treatments grade 2 granulocytopenia was observed while four patients (17%) developed grade 2 neuropathy. Seven patients (29%) achieved a partial response and five (21%) had stable disease. Paclitaxel 90 mg/m(2) per week as salvage treatment is well tolerated and has shown promising activity in patients with NSCLC who progress after platinum treatment.

One hundred eighteen patients with various malignancies received a total of 847 vinorelbine (VNR) infusions, during 25 of which episodes of vinorelbine phlebitis occurred (1 in each of the 25 patients concerned). Venous irritation was graded with reference to the scale devised by Rittenberg et al. To prevent these 25 patients against further venous toxicity, we pretreated them with cimetidine 200 mg i.v. prior to VNR administration in subsequent cycles of chemotherapy. In most (19, or 76%) complete prevention of recurrent phlebitis was observed, while partial prevention was observed in 5 patients (20%). Treatment was unsuccessful in 1 patient. In 127 VNR infusions given after cimetidine prophylaxis only 7 (6%) episodes of phlebitis occurred. These data show that i.v. administration of cimetidine prior to vinorelbine infusion can successfully prevent recurrence of phlebitis in patients who have shown venous irritation upon prior VNR treatment, at a rate of 94%.

Purpose: To assess the antitumor efficacy and safety of a vinorelbine and cisplatin combination in patients with metastatic breast cancer previously treated with anthracyclines.Patients and methods: Fifty-three patients with assessable metastatic breast cancer with previous exposure to anthracyclines (adjuvant n = 6, palliative n = 47) were studied. Cisplatin 75 mg/m(2) on day 1 was given followed by 25 mg/m(2) vinorelbine (VNR) on days 1 + 8, in a five-min i.v. infusion. Courses were repeated every three weeks on an outpatient basis. Treatment continued until disease progression, excess toxicity or patient refusal. Patients were classified according to their response to anthracyclines: anthracycline refractory patients were patients who had never responded under an anthracycline regimen. Anthracycline resistant patients were either metastatic patients who progressed within four months of completing anthracycline-based chemotherapy or patients who progressed within six months of completion of an anthracycline adjuvant treatment. Patients who progressed four months after the end of an anthracycline regimen in metastatic setting or six months after the end of an anthracycline regimen in adjuvant setting were considered as patients previously treated with anthracyclines and were called 'relapsed'.Results: Four patients (8%) achieved a complete response (CR) and twenty-two patients (41%) achieved a partial response (PR) with an overall response rate (OR) of 49% (95% confidence interval (CI): 35-63). Stable disease (SD) was observed in five patients (9%), twenty-two patients had progressive disease (PD). Responses according to previous sensitivity to anthracycline were as follow: 5 refractory patients achieved a PR from 14 patients (36%). Seven of sixteen resistant patients responded (44%), six with PR and one with CR. Among 23 'relapsed' patients, 14 responses were observed (61%), with 3 CR and 11 PR. There was no statistical difference in RR among the three groups. The median duration of response for all patients was 7 months, the median time to progression (TTP) 5 months and median overall survival 12 months.All patients were assessed for toxicity. The main toxicity was neutropenia grade 3 and 4 in 49% of patients. Febrile neutropenia requiring hospitalization was uncommon (2 patients). There were no treatment related deaths. Despite potential overlapping neurologic toxicities of the two drugs, only eight patients (15%) developed neuropathy, which was, however, mild (grades 1 and 2).Conclusions: This cisplatin-VNR regimen is well tolerated and active in patients who failed anthracyclines. The response rate, TTP and survival data are engouranging and indicate that cisplatin-VNR may have a place as second-line treatment alternative to taxanes or other less active regimens. If these results can be verified in multi-institution trials, this combination of drugs would merit investigation as first-line therapy in this patient population.

PURPOSE:The aim was to study the effectiveness of docetaxel (Taxotere) in patients with advanced breast cancer treated previously with polychemotherapy.PATIENTS AND METHODS:Forty-nine patients received docetaxel (100 mg/m2; 1-h i.v. infusion) and corticosteroid premedication. Forty-one patients who had received previous anthracycline treatment were divided into anthracycline-refractory and anthracycline-resistant (early and late) groups.RESULTS:Of 45 evaluable patients, 66.7% had a partial response (PR) and 2.2% a complete response (CR), giving an overall response rate (ORR) of 68.9%. The ORR in anthracycline-refractory patients was 60% versus 82.6% in anthracycline-resistant patients; the difference was not significant. The ORR in early-resistance patients was 62.5% versus 93.4% in late-resistance patients (0.05 < P < 0.1). The median response duration and overall survival was 8 months (range, 4-23 + months) and 11.5 months (range, 4-31 + months), respectively, in 39 patients treated previously for metastatic disease. For 295 courses, grade 3/4 neutropenia developed in 28.6% of patients (12.5% of courses) and was febrile in 26.5% of patients (6.1% of courses), including one septic death. Hypersensitivity reactions (HSR) developed in 16.3% of patients, and fluid retention developed in 34.7% of patients (11.9% of courses).CONCLUSIONS:Docetaxel is an active second-line drug in advanced breast cancer. The time of relapse after cessation of anthracycline treatment may be a significant prognostic factor.

Purpose: The aim of this study is to compare various time schedules of granulocyte colony-stimulating factor (G-CSF) treatment in a clinical model of patients who received high-dose cyclophosphamide (HDCY 45 g/m2) for the treatment of an underlying malignancy in order to investigate the optimal time (preemptive vs. supportive) of G-CSF initiation upon the incidence and duration of cytopenias and related parameters, such as incidence of febrile episodes, antibiotic use, duration and cost of G-CSF administration and overall clinical benefit and cost effectiveness of various schedules used. Patients and Methods: Seventy-two courses were given in a sequential cohort study. G-CSF was administered either 24, 48, 72, 96 h after chemotherapy (preemptive treatment) or upon the onset of leukopenia (WBC ≤1,000/µl) (supportive treatment). Study parameters were compared among the various groups as well as to a control group who received HDCY without G-CSF support. Results: (1) Patients who received G-CSF early (24, 48 h) had a shorter duration of leukopenia (WBC ≤1,000/µl) compared to those who received G-CSF at a later stage (72, 96 h) or as supportive treatment (p < 0.05). However the duration of neutropenia (ANC ≤500/µl) or thrombocytopenia (platelets ≤20,000/µl) was not affected by the different time schedules of treatment. (2) Patients who received G-CSF early (up to 72 h) had less febrile days with neutropenia in comparison to late treatment (>96 h), supportive and control groups (p < 0.05). The cost of antibiotics was also in favor of the early treatment group. The median duration of febrile days of the delayed (>72 h) treatment groups and antibiotic cost was similar to those in patients who did not receive G-CSF at all. (3) When G-CSF was given preemptively a shorter time was required to reach normal WBC (5,000/µl) in comparison to the sup- portive and control group. This was due to a prolonged WBC recovery rather than to an early onset of leukopenia (tail effect). A delayed leukopenia recovery occurs as administration of G-CSF is delayed. (4) As a result the required length of G-CSF treatment to reach normal WBC (5,000/µl) was shorter in the early treatment group and the cost from G-CSF use was less in that group in comparison to the late (>72 h) and supportive groups which indicated an increased cost without clinical benefit over controls. Conclusions: G-CSF administration after HDCY has a similar effect upon the incidence and duration of severe leukopenia and thrombocytopenia. However, severe leukopenia is shorter when G-CSF starts up to 72 h after HDCY. The length of G-CSF administration and its cost is also in favor of early initiation of treatment as well as the number of febrile days and antibiotic use. Delayed (>72 h) or supportive treatment indicate more febrile episodes, antibiotic use and higher cost when compared to the early groups. Late (>72 h) or supportive G-CSF administration in this study indicates no benefit versus no treatment in relation to length of leukopenia, febrile days, antibiotic use and overall treatment cost.