To examine whether the concomitant administration of a gonadotrophin-releasing hormone agonist (GnRHa) during combination chemotherapy to young women with lymphoma may facilitate preservation of gonadal function, a prospective clinical protocol was undertaken in 18 cycling women with lymphoma, aged 15-40 years. Thirteen patients suffered from Hodgkin disease (HD) and 5 from non-Hodgkin lymphoma. After informed consent a monthly injection of depot D-TRP6-GnRHa was administered for a maximum of 6 months starting prior to chemotherapy. Most of these patients (15/18) were treated with the MOPP/ABV(D) combination chemotherapy followed by mantle field irradiation in 10 patients. Hormonal profile [luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol, testosterone, progesterone, insulin-like growth factor (IGF)-1, prolactin] was taken before the GnRHa/chemotherapy co-treatment, and monthly thereafter until resuming spontaneous ovulation and menses. This group of prospectively treated lymphoma patients was compared to a matched control group of 18 women (aged 17-40 years) who have been treated with chemotherapy, mostly MOPP/ABV (14/18), with (11) or without (7) mantle field radiotherapy. Fourteen had Hodgkin's and four non-Hodgkin's lymphoma. Gonadal function was determined clinically, hormonally (LH, FSH, oestradiol, progesterone), and sonographically. Two of the patients in each group died from refractory disease. Of the remaining 16 patients, 15 (93.7%) resumed spontaneous ovulation and menses within 3-8 months of termination of the combined chemotherapy/GnRHa co-treatment. In contrast, only seven (39%) of the 18 similarly treated patients in the control group (chemotherapy without GnRHa) resumed ovarian cyclic activity (regular menses). The other 11 experienced premature ovarian failure (POF) (61%). Out preliminary data suggest a possible significant protective effect of GnRHa co-treatment with chemotherapy from irreversible ovarian damage (POF).
Background. Most current lymphoma protocols limit vincristine dose to 2 mg per single dose. Because a lower dose of vincristine may be associated with poorer outcome, there is some rationale to increase the dose of vincristine. Methods. The feasibility of full dose vincristine (i.e., 1.4 mg/m2 without 2‐mg dose limit) was prospectively evaluated in lymphoma patients treated with various combinations. After an initial dose of 1.4 mg/m2, patients were carefully monitored, and dose was modified according to toxicity. Results. One hundred and four consecutive patients (31 with Hodgkin's disease and 73 with non‐Hodgkin's lymphoma), aged 18–78 years were evaluated. The first dose was greater than 2 mg in 90% of the patients. The mean actual dose (percent of projected dose) was 100% in the first course and gradually decreased to 64% in the eighth course. The mean actual dose intensity of vincristine (percent of projected dose intensity) during the initial six cycles of prednisone, methotrexate, calcium leucovorin, doxorubicin, cyclophosphamide, etoposide, and mechlorethamine, vincristine, procarbazine, prednisone (ProMACE/MOPP), cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and MOPP/doxorubicin, bleomycin, and vinblastine (MOPP/ABV) was 82% and MOPP/doxorubicin, bleomycin, and vinblastine was 82%, 83%, and 87%, respectively. Symptoms of neuropathy developed in 92% of the patients and were usually of mild or moderate severity. Toxicity included World Health Organization (WHO) Grades 3 and 4 constipation in 10 (10%), and WHO Grade 3 peripheral neurotoxicity in 16 (15%) patients. Rapid improvement was usually noticed within a few weeks after withdrawal of vincristine. The median duration of symptoms from discontinuation of vincristine was 3 months for paresthesiae and motor weakness and 5 months for muscle cramps. Conclusions. Full dose vincristine in lymphoma protocols is feasible but is associated with increased toxicity. The therapeutic advantage of full dose vincristine has yet to be proven.
Cord compression was noted at presentation in 10 of 453 (2.2%) previously untreated non-Hodgkin's lymphoma patients seen at the Northern Israel Oncology Center between 1968 and 1983. A prodromal phase of local back pain occurred in eight patients, persisting up to 1 year, followed by a second phase of rapidly progressive signs of cord compression. Five of the ten patients presented with primary spinal epidural involvement (Stage IE), whereas the others had Stage IIE and IIIE (one patient each) and Stage IV, with bone and bone marrow involvement (three patients). All patients had unfavorable histologic diagnoses, mostly of the intermediate grade malignancy types according to the Working Formulation. The patients were treated by radiotherapy (two patients), chemotherapy (three patients), or both modalities (five patients). Seven of the ten patients achieved complete remission, but four of them have subsequently had relapses (two patients in bone, one in central nervous system, and one in mediastinum). The 5-year actuarial survival and 3-year relapse-free survival were 66% and 32%, respectively. Median survival has not been reached after a mean follow-up of 34 months. Non-Hodgkin's lymphoma with spinal epidural involvement at presentation is an aggressive disease. An intensive treatment combining irradiation with chemotherapy, and surgery as needed, is suggested in order to achieve good local response and long-term survival.
Ninety-five newly diagnosed patients with diffuse large cell lymphoma (DLCL) treated by cyclophosphamide (CTX), doxorubicin (ADM), vincristine (VCR), and prednisone (CHOP regimen) chemotherapy were evaluated for survival factors including dose intensity (DI). DI calculations were done for the initial cycles needed to achieve maximal response. The medians of the relative DI for CTX, ADM, and VCR were 0.9, 0.86, and 0.79, respectively. The median of the average relative DI (ARDI) was 0.83 (range, 0.28 to 1.14). The univariate analysis of potential prognostic variables showed that the following significantly decreased the survival rate: age older than 60 years (P = 0.0005), Stage III to IV (P = 0.02), male sex (P = 0.03), and all four DI variables (CTX, ADM, VCR, and ARDI) less than the median (P = 0.01 to 0.0001). A multivariate analysis by the stepwise proportional hazards model of Cox indicated that the factors predicting a poor prognosis were ARDI less than the median (P = 0.0003) and age older than 60 years (P = 0.02). A multivariate survival analysis of those who achieved complete remission showed ARDI less than the median (P = 0.0003), CTX less than the median (P = 0.02), and Stage III to IV (P = 0.02) to be the most negative factors regarding survival. In conclusion, a high DI in the initial cycles of CHOP chemotherapy for DLCL has a significant positive impact on survival.
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