Full dose vincristine (without 2-mg dose limit) in the treatment of lymphomas

Abstract

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.

Full Dose Chop Chemotherapy in Elderly Patients with Non-Hodgkin's Lymphoma

“…The toxicity was acceptable, and there was no toxic death. It is worth mentioning that full-dose vincristine did not increase neurotoxicity in the elderly, compared to younger patients, as recently reported to us (30). Treatment results compare favorably with those reported elsewhere, although the follow-up period is short.…”

Phase II Study of Vincristine Sulfate Liposome Injection (Marqibo) and Rituximab for Patients With Relapsed and Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma in Need of Palliative Therapy

“…In a comprehensive evaluation of nonliposomal VCR-related neuropathy, Haim et al reported a 92% peripheral neuropathy AE rate, 78% paraesthesia rate, and 10% Grade 3 and 4 constipation rate as a result of nonliposomal VCR 1.4 mg/m 2 dosed every 21 days as part of a multidrug regimen in previously untreated and VCR-naive NHL patients. 19 In our study, VSLI 2.0 mg/m 2 every 14 days in heavily pretreated, VCR exposed, and neuropathy-prone patients was associated with a 23% peripheral neuropathy rate, 32% paraesthesia rate, and 5% Grade 3 constipation rate. These AE rates likely reflect the optimized pharmacokinetic properties of liposomal encapsulated VCR in VSLI.…”

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

“…Indeed, higher doses of Marqibo were able to be administered to patients compared with standard vincristine (Hagemeister et al, 2013;O'Brien et al, 2013). As vincristine in excess of 2 mg has been associated with severe neuropathy, a standard vincristine dose of 1.5 mg/m 2 has a dose cap of 2.0 mg per single administration, regardless of the total body surface area (Haim et al, 1994). This helps limit the amount of vincristine exposed to patients with a total body surface area .1.33 m 2 (Raj et al, 2013).…”