Activity and safety of dose-adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab in very elderly patients with poor-prognostic untreated diffuse large B-cell non-Hodgkin lymphoma.

BACKGROUND: This study was designed to assess the activity and safety of dose-adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab (DA-POCH-R) in elderly patients with poor-prognostic untreated diffuse large B-cell non-Hodgkin lymphoma (DLBCL). METHODS: From April 2006 to November 2009, 23 patients, aged ≥70 years, with an age-adjusted International Prognostic Index (IPI) of 2 or 3, were enrolled. Only patients with left ventricular ejection fraction (LVEF) ≥50% were allowed. The DA-POCH-R regimen was administered every 3 weeks for a minimum of 6 and a maximum of 8 cycles. RESULTS: Median patient age was 77 years (range, 70-90 years); 83% of patients had Ann Arbor stage III to IV disease. Median LVEF at baseline was 62%. Four (17%) patients had a history of abnormal cardiovascular conditions. Twenty-one (91%) patients were evaluable for response. The overall response rate was 90%, with a complete response rate of 57%. The 3-year overall survival and event-free survival rates were 56% and 54%, respectively. Neutropenia (48%) was the most frequent grade 3 to 4 adverse event (AE); no grade 3 to 4 cardiac AEs were observed. CONCLUSIONS: DA-POCH-R was an active and safe combination therapy for patients aged ≥70 years with poor-prognostic untreated DLBCL. This regimen was a reasonable alternative for elderly patients who were not considered to tolerate standard R-CHOP treatment.

Hepatic artery administration of docetaxel in liver metastases from breast carcinoma: a feasibility study.

AIMS AND BACKGROUND: Taxanes are largely metabolized and almost exclusively excreted in the feces by the liver through the biliary pathway, thus providing a rationale for investigating the activity of their hepatic artery delivery in case of liver metastases. STUDY DESIGN: The aim of this study was to assess the feasibility of administering docetaxel via the hepatic artery in advanced breast cancer patients in whom the liver was the only or the predominant site of metastatic involvement. The dose was increased cycle by cycle in a prospective manner. RESULTS: Ten eligible patients were enrolled. The median administered dose in the last cycle was 65 mg/m2 (range, 40-100 mg/m2). The treatment was generally well tolerated, and only one patient stopped after two cycles because of toxicity. Four of the 9 eligible patients with assessable liver tumors achieved an objective response. After a median follow-up of 41 months, 4 of the 10 eligible (and 11 treated) patients were alive with a median overall survival of 46 months. CONCLUSIONS: The administration of docetaxel via the hepatic artery is feasible. The highly interesting response and survival results observed in this limited series of patients warrant further studies.

P-CHOP: cisplatin (P) added to the standard CHOP regimen as first-line treatment for aggressive non-Hodgkin lymphoma: a single-institution phase II study.

We designed the P-CHOP regimen, which involves the addition of cisplatin (P) to the standard CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen, and investigated its activity and its toxicities in a single institution phase II study. Twenty-two consecutive patients with untreated, aggressive, stage I-IV non-Hodgkin lymphoma were enrolled in the study. Cisplatin was administered at a dose of 40 mg/m2 on days 1 and 2, every 3 weeks; the dose and schedule of the other agents were identical to those used in the standard CHOP regimen. The complete remission (CR) rate was 86% in eligible and 80% in all the treated patients, which compares favorably with the CR rates of two recent randomized studies of CHOP versus other regimens. P-CHOP is an innovative regimen for the front-line treatment of aggressive non-Hodgkin lymphoma. It is feasible and warrants further research, which would ideally take the form of a randomized comparison of P-CHOP and CHOP, possibly with the addition of rituximab in both arms.

Gemcitabine and oxaliplatin: a safe and active regimen in poor prognosis advanced non-small cell lung cancer patients.

BACKGROUND AND AIMS: Most patients with non-small cell lung cancer (NSCLC) cannot tolerate a cisplatin-based chemotherapy because of old age, general conditions, and/or multiorgan metastatic sites. Oxaliplatin is active in NSCLC, offers advantage in terms of toxicity, and shows synergism with gemcitabine. The aims of this phase II study were to evaluate the response rate and toxicity of the gemcitabine-oxaliplatin combination in patients with advanced NSCLC and poor prognosis. METHODS: Patients were given a gemcitabine infusion (1000 mg/m(2) over 30 min on days 1 and 8) followed by oxaliplatin (65 mg/m(2) over 120 min on days 1 and 8) every 21 days for six cycles. RESULTS: Thirty-two patients with poor-prognosis advanced NSCLC received 136 cycles. There were 25 males and seven females, and the median age was 65 years (range 29-76). Fifty-six percent of patients had adenocarcinoma, and 31% had squamous cell carcinoma. Sixty-six percent of patients had stage IV disease, and 34% had stage IIIB disease. Eastern cooperative oncology group (ECOG) performance status was 2-3 in 50%, 1 in 44%, and 0 in 6% of patients. Eight patients (25%) had been previously treated with cisplatin or carboplatin. All patients were symptomatic. Of the 32 patients who received study drug, five (16%) achieved partial response, six (19%) had minor response, three (9%) had stable disease, and 15 (47%) progressed. The median overall survival was 27 weeks. Thirty-one patients were evaluable for toxicity: seven patients (23%) had grade 3-4 thrombocytopenia with no bleeding; four patients (13%) had grade 3-4 neutropenia with no febrile neutropenia, and three patients (10%) had grade 3 anemia. Two patients (6%) had grade 3, and six patients (19%) had grade 1-2 neurotoxicity. CONCLUSION: The combination of gemcitabine and oxaliplatin seems to be well tolerated and active in patients with poor prognosis advanced NSCLC and deserves further evaluation in phase II clinical trials.

Compliance and outcomes in locally advanced head and neck cancer patients treated with alternating chemo-radiotherapy in clinical practice.

BACKGROUND AND AIMS: To evaluate the feasibility in clinical practice of alternating chemo-radiotherapy in locally advanced head and neck cancer patients. PATIENTS AND METHODS: From August 1993 to April 1998 at the Division of Medical Oncology of Parma, 48 consecutive patients were observed, and 38 (79%) started the Merlano chemo-radiotherapy. The characteristics of the patients were: males (32, 84%); median age, 57 years; PS <2 (32, 84%). The primary sites were the oropharynx (18, 47%), oral cavity (8, 21%), hypopharynx (7, 19%), larynx (5, 13%); stage IV disease was present in 29 (76%) patients. Twenty-five (66%) patients were married, and 24 (63%) resided outside of the city. RESULTS: The compliance was very low: 21 patients (55%) performed all the programmed cycles of chemotherapy, whereas only 5 patients (13%) performed the chemo-radiotherapy at full doses without any delay. The objective responses were 3 (8%) complete and 21 (55%) complete plus partial responses. Failures were 2 (5%) stable disease and 2 (5%) progressive disease, and the response was not assessable in 10 (26%). The median duration of the response was 8 months. The median overall survival and the time to progression were 18 and 13 months, respectively; the 5-year overall and relapse-free survival were 36% and 26%, respectively. Nine (24%) patients were still alive as of August 30, 2001, 8 (21%) of them without progression. Twenty-six patients (68%) died with a local-regional relapse. One patient (3%) died for a second cancer. Grade 3-4 hematologic toxicity was leukopenia (n = 25, 66%) and thrombocytopenia (n = 9, 24%); grade 3-4 non-hematologic toxicity was diarrhea (n = 3, 8%) and mucositis (n = 2, 5%). Two patients (5%) died for intestinal infarction and perforation possibly related to treatment. CONCLUSIONS: Compliance to the chemo-radiotherapy was very poor. The response rate was lower than that reported in clinical trials, whereas overall survival was comparable. The alternating chemo-radiotherapy is a very complex treatment that cannot be easily applied in clinical practice; a careful selection of patients is mandatory not only considering oncologic and medical criteria, but also the level of awareness of the patient and his family.