Patients Received Maintenance Chemotherapy Research Articles

A phase I trial of erlotinib, gemcitabine and radiation for patients with locally advanced, unresectable pancreatic cancer

4107 Background: Pre-clinical data indicates that inhibition of EGFR potentiates the effect of gemcitabine (gem) and radiation (RT) in pancreatic cancer cell lines. Based on this data, we are conducting a phase I trial to determine the maximal tolerated dose (MTD) of erlotinib (Tarceva), an oral EGFR TKI, in combination with gemcitabine and RT in patients with histologically-proven, locally-advanced unresectable pancreatic adenocarcinoma. Methods: Cohorts of 3–6 patients received escalating doses of erlotinib (100mg, 125mg) with gem (40mg/m2, biw) and RT (50.4 Gy in 28 fractions to the primary and regional nodes.) Four weeks following completion of chemoradiation (CRT), patients received maintenance chemotherapy with gem 1000 mg/m2 (d1, 8 every 21 days) and erlotinib 100 mg daily for 4 cycles. Eligibility criteria included laparoscopically-staged, locally-advanced disease; no prior therapy; normal organ and bone marrow function; ECOG PS ≤ 2. Toxicity was assessed during and for 2 weeks following CRT Results: Nine patients have been enrolled: M:F 3:6, median age 58 (range 45–79), median PS 1. Three patients received erlotinib at 100mg and 6 patients at 125mg. Common non-heme toxicities included fatigue, abdominal pain, nausea/vomiting, weight loss and rash. Grade 3/4 leukopenia (n=4) and thrombocytopenia (n=2) was observed only at erlotinib 125 mg. One patient at 100 mg (fever) and 2 patients at 125 mg (fever, N/V) were hospitalized while receiving CRT. DLT at the 125 mg dose level was observed in 2 patients: persistent myelosuppression which delayed completion of treatment beyond 7.5 weeks (n=1) and grade 3 transaminitis (n=1). Following CRT, 8 patients were evaluated for response radiographically: (7 SD, 1 POD). Of 6 patients with an elevated CA19–9 at baseline, 4 experienced a decrease by > 50%. One patient was referred for exploratory laparotomy and underwent an R1 resection. We are treating 10 additional patients at the MTD to better define toxicity and efficacy. Conclusions: The MTD of erlotinib in combination with gem 40mg/m2 biw and standard RT is 100mg daily. Correlative tissue stained by IHC for EGFR, pEGFR, HER2/neu, pAKT and PTEN will be presented. (Supported by ACS MRSG 04–239-01-CCE) No significant financial relationships to disclose.

Persistent human parvovirus B19 infection in children under maintenance chemotherapy for acute lymphocytic leukemia.

To report on B19 infection management and chemotherapy schedule consequences in five children treated for acute lymphocytic leukemia (ALL). Between May 2001 and February 2002, five patients between 4 and 12 years of age, receiving maintenance chemotherapy for ALL, presented with symptoms suggesting B19 infection (pallor, fatigue, petechiae and pancytopenia in four patients; generalized rash in two patients; acute hepatitis in one patient). Qualitative polymerase chain reaction (PCR) on peripheral blood was used for diagnosis and follow-up of infection; quantitative PCR was used for viral load measurement. Intravenous nonspecific high-dose immunoglobulin therapy was administered until PCR was negative. Qualitative B19 DNA was found in the peripheral blood of all patients, confirming the infection. Viral load at diagnosis ranged from 10 to 10 particles/mL blood. B19 DNA was detectable in four patients at 45, 21, 40, and 44 weeks, respectively. Chemotherapy was delayed in all patients. No clear benefit of intravenous immunoglobulin was noted. Infection with B19 is rarely reported in patients with ALL, but it should be suspected when unexplained pancytopenia occurs during chemotherapy. Persistent B19 infection remains a challenge in the management of patients receiving maintenance chemotherapy for ALL, as no specific therapy such as a specific immunoglobulin or vaccine exists. The role of viral load measurement needs to be established in terms of its use in follow-up and evaluation of the therapeutic response.

A correlational evaluation of tiredness and lack of energy in survivors of haematological malignancies.

Data about tiredness and lack of energy from 91 bone marrow transplant (BMT) survivors and 73 patients receiving maintenance chemotherapy were collected. A correlational evaluation revealed that these two distressing symptoms were associated with physical, psychological, cognitive and social dimensions of quality of life (QOL). A stepwise regression model for BMT survivors showed that both tiredness and lack of energy could be predicted by the combined effect of difficulty concentrating and overall psycho-social adjustment. In addition, dizziness was also influencing tiredness. Lack of energy was predicted in the chemotherapy patients with the combined effects of adjustment to social environment, shortness of breath and psychological symptom distress (R2 = 0.80). In the same group of patients, tiredness was explained by a model consisting mainly of physical symptoms and cognitive symptoms, associated probably with the chemotherapy they were receiving, together with social adjustment (R2 = 0.86). The identification of the reasons behind tiredness and lack of energy in cancer patients, broadly defining fatigue and commonly experienced by them, will have implications for both patient education and the design of appropriate interventions to combat fatigue.

Perceived social support, family environment and psychosocial recovery in bone marrow transplant long-term survivors

This report examines perceptions of social support and family dynamics in bone marrow transplant (BMT) long-term survivors, as part of a larger study examining issues of quality of life and psychosocial adjustment in this patient group. Ninety one BMT survivors participated in the study. Their responses were compared with those of a matched control group of 73 patients receiving maintenance chemotherapy (MC). The results indicated that the BMT group received more social support than the MC group. Main sources of support were the patients' immediate family members. No significant differences in the typology and dynamics of family environments were observed between groups. However, the groups were significantly different compared with healthy, non-distressed families in cohesion, control and conflict. It was of importance to note that a considerable number of BMT subjects reported at least one nurse as a person who provides support to them, indicating the potential important role of nurses in the psychosocial adjustment of BMT long-term survivors. Strong family relationships were associated in both the BMT and MC groups with significantly better adjustment with respect to their domestic, extended family or social environment, and psychological distress. Social support and family relationships might be two of the main spheres of life contributing to higher levels of quality of life, and their important role as a stressor-filter is highlighted.

Persistence of Immunity to Varicella in Children with Leukemia Immunized with Live Attenuated Varicella Vaccine

To determine the safety and efficacy of varicella vaccine, we studied 437 children in remission from leukemia who were immunized with live attenuated varicella virus. Three hundred one of the patients received two doses of vaccine and 136 received a single dose of vaccine from 1 of 10 lots from two manufacturers. The patients have been followed for an average of three years (range, one to six). Seroconversion occurred in 88 percent of the 437 children after the first dose of vaccine and in 98 percent after one or two doses. The proportions of patients who were seronegative after one, three, and five years were 20, 25, and 30 percent, respectively, with little change over time in the geometric mean titers of specific antibody (6.3, 6.5, and 5.7, respectively). Chickenpox has been documented in 36 vaccinated patients (8 percent) who had 3 to 640 vesicles (mean, 100), mild illness, and no complications. Of the 83 vaccinated patients exposed to varicella within their families, 11 had chickenpox; the attack rate was 14 percent (8 percent among seropositive patients, 29 percent among seronegative patients). There was no relation between the time since vaccination and either the attack rate or the severity of the breakthrough illness. Two doses of vaccine appeared to be no more effective than a single dose. Of the 372 patients receiving maintenance chemotherapy when immunized, 149 (40 percent) had a rash, which was treated with acyclovir in 16 children (4 percent) and became a severe febrile illness in 4. These reactions were not fatal and were all associated with vaccine lots, the use of which has since been discontinued. We conclude that in children in remission from leukemia, varicella vaccine is safe and induces an immunity to chickenpox that persists for more than three years.

Results of a combined chemo-radiotherapeutic program in 61 patients affected by small cell lung cancer.

Sixty-one patients affected by small cell lung cancer (SCLC) entered in the study. Eighteen had limited disease and 43 extensive disease. Treatment consisted of: induction chemotherapy with 3 courses of CAV (cyclophosphamide, adriamycin, vincristine) in limited disease patients or 2 courses of CAV plus 2 courses of DDP-VP16 (cisplatin, etoposide) in extensive disease patients, followed by chest radiotherapy and CNS prophylaxis in responsive patients. Subsequently, responders and stable patients received maintenance chemotherapy by the alternation of cycles of CAV, DDP-VP16 and C'MP (CCNU, methotrexate, procarbazine), which lasted 1 year or until relapse. Four of 17 limited disease patients (23%) obtained a CR and 11 (65%) a PR; their median survival was 11 months (range, 2+-36+). One of the 7 extensive disease patients (3%) achieved a CR and 19 (51%) a PR; their median survival was 6 months (range, 1-22). Median duration of response was 12 months for CR and 5 months for PR. Responders (CR and PR) survived 11.5 months versus 3.5 months for failures (P less than 0.05); 3/61 (5%) showed long-term survival, in the absence of disease. The overall median survival was 7 months (range, 1-36+). The main toxic effects were myelosuppression and vomiting (WHO grade 3). From our results, this program does not offer further substantial gains in patients with SCLC.

EORTC trial non-Hodgkin lymphomas

Results of an EORTC trial (20751) in non-Hodgin lymphomas are presented. Patients were treated in the same way independent of the histological type. There were 468 patients in the study of whom 124 patients were in stage I ( 85% 5 year survival), 57 in stage II (55%), 121 in stage III (55%) and 166 in stage IV (45%). Using the Kiel classification the low grade lymphomas were subdivided into two categories: those with a follicular ( 80% 5 year survival) and with a diffuse cell pattern ( 50% 5 year survival) with an intermediate prognosis compared with the high grade lymphomas ( 35% 5 year survival). Treatment was stratified according to stage. In stage I regional radiotherapy was given followed by randomization for maintenance chemotherapy with Vincristine, Cyclophosphamide and Prednisone. No influence in survival was seen ( 85% at 5 years), although disese free survival was better in the maintenance chemotherapy group ( 75% vs 55% at 5 years). In stage II regional radiotherapy was followed, after randomization, by transdiaphragmatic irradiation, all patients received maintenance chemotherapy. The group was too small to draw conclusions about the effect of this treatment. Primary radiotherapy in stage II disease with diffuse histology gave bad results. Patients in stage III and IV were treated with 8 courses of chemotherapy with Adriamycin, VM 26, Cyclophosphamide and Prednisone, given in two different time schedules. Iceberg radiation was then given to areas with initially large or slowly responding disease. All patients had maintenance chemotherapy. No difference was found for the 2 chemotherapy schedules in remission rate, disease free interval and survival. In stage III and IV patients with a follicular lymphoma have a longer relapse free interval and total survival ( 39% and 68% at 5 years) compared with those with lymphoma diffuse histology ( 19 and 30% at 5 years). Patients with stage IV disease due to bone marrow involvement only had a better prognosis compared with stage IV disease for other reasons.

Chemotherapy-radiotherapy versus chemotherapy in Hodgkin's disease with bone marrow involvement. Retrospective analysis of 32 cases.

A retrospective analysis was performed on 32 patients suffering from Hodgkin's disease with bone marrow involvement treated between 1972 and 1976. After 6 courses of chemotherapy (MOPP for 25 patients), we observed 20 complete remissions (62.5%), 8 lymph node partial remissions (bone marrow sterilization but persistence of pathological lymph nodes) and 4 failures. among the 28 complete or partial responders, 17 received maintenance chemotherapy alone, 9 were submitted to 40 Gy and 2 to 20 Gy irradiations. 15 patients died and 8 relapses occurred - all in previously involved lymph node areas. Survival of complete and partial responders is significantly different (p = 0.01) according to whether they received maintenance chemotherapy alone (34.5%) or irradiation (75.7%). Disease-free duration is also significantly different (p = 0.05) according to whether the patients received maintenance chemotherapy alone (42.1%) or 40 Gy irradiation (100%).