1299
Letters
EurJ Cancer, Vol. 28A, No. 617, p. 1299,199Z. Pnnred in GreatB&am 091%1947192$S.W + 0.00 0 1992 I’ergamon Press Ltd
Eur3 Cancer, VP/. Z8A, No. 617, p. 1299, 1992. Pnnud I” GrearBnratn G96&1947l92$5.00 i 0.00 0 1992 Pegama l’ress Ltd
Prolonged Thrombocytopenia After Procarbazine “Overdose” M. Hadjiyanni,
K. Valianatou, and B. Seitanidis
M. Tsilianos
MMAF for Advanced Gastric Cancer J. Wils and H.O. Klein ANDERSONet al.
report a phase II study with MMAF combination chemotherapy in 65 patients with advanced gastric cancer [ 11. MMAF is sequential high-dose methotrexate and 5-fluorouTHE MAJORtoxicity of procarbazine is dose-related reversible racil(5-FU) on day 1 with leucovorin rescue starting on day 2 haemopoietic suppression with leukopenia and thrombocytoand doxorubicin plus mitomycin on day 14. In fact, this is the penia in a significant percentage of the patients when it is given FAMTX regimen with additional mitomycin, 4 mg/m2. They at maximum dose of 3 mg/kg for 14 days [ 1, 21. achieved a response rate of 29%, including 6% with a complete We describe a patient with Hodgkin’s disease who received response and a median survival of 7 months without major procarbazine for 25 days (150 mg daily) and who developed toxicity. prolonged thrombocytopenia. These results are not different from those reported by the A 29-year-old male with stage IIIA lymphocyte predominance EORTC Gastrointestinal Tract Group in a multi-institutional Hodgkin’s disease started MOPP in July 1985 and inadvertantly phase II study with FAMTX (33% response rate and 6 months continued 150 mg procarbazine daily for 25 days. His blood median survival in 66 patients), with the exception of toxicity count remained normal, although the platelet count fell from which was higher in the EORTC study, mostly due to non230 x lo911pretreatment to 140 x lo9 post-treatment. adherence to the protocol [2]. A second course of full dosage MOPP was started on 9 August In a subsequent phase III study, the EORTC Gastrointestinal 1985. When he returned for the third cycle the platelet count Tract Group compared FAMTX with FAM in 213 patients and was 79 x 109/1. Chemotherapy was discontinued after the first found the FAMTX regimen to yield a significantly better week because of thrombocytopenia which persisted for the response rate and survival [3]. An updated survival comparison subsequent 4 years with platelet counts ranging from 20 x 109/1 in this study shows a median survival of 44 weeks for FAMTX to 30 x 109/1.A bone marrow aspiration, 20 days after chemoand of 29 weeks for FAM (P = 0.002). No imbalance between therapy, showed reduced cellularity with some megaloblastoid the groups could be detected in a Cox regression model. changes in the erythroblasts, a shift to the left in the granulocyte Therefore, we question the conclusion by Anderson et al. that series and megakaryocytes almost absent. MMAF did not improve the response or survival compared with No further chemotherapy was given. Radiotherapy was given FAM. The authors did not compare their regimen with FAM to the mediastinum where the main bulk of his disease was. He and no particular conclusion can be drawn from comparison received 18.5 Gy and discontinued treatment against medical with other phase II studies. We feel that MMAF as defined by advice. At that time haemoglobin was 10.8 gidl, white cells Anderson et al. is not essentially different from FAMTX, which were 4.5 x lo911 with normal differential, and platelets were is clearly superior to FAM. FAM should no longer be advocated 27 x 10’11.The platelet count started to recover in early 1989 for advanced gastric cancer. and by April 1991 the count was 350 x 10911.The patient remains in complete remission. The likely explanation for the patient’s thrombocytopenia is the protracted treatment with procarbazine with depletion of marrow reserves and suppression of committed megacaryocytic Anderson H, Scarffe JH, Ranson M, et al. MMAF for advanced stem cells. Selective toxicity of megakaryocytes to procarbazine gastric cancer. EurJ Cancer 1991,27,1234-1238. Wils, J, Bleiberg H, Dalesio 0, et al. An EORTC gastrointestinal has not been reported previously.
1. Henry MC, Marlow M. Preclinical toxicologicstudy of procarbazine (NSC-77213).CancerChem Rep 1973,4,97-102. 2. Stolinsky DC, Solomon J, Pugh RI’. Procarbazine HCL in Hodgkin’s
disease, reticulum cell sarcoma and lymphosarcoma. Cancer, 1970, 26,9&t-990.
Correspondence to B. Seitanides. The authors are at the Department of Clinical Haematology, Metaxas Memorial Hospital of Piraeus, 5 1 Botassi str., 185 37 Piraeus, Greece. Received 2 Dec. 1991; accepted 13 Dec. 1991.
group evaluation of the combination of sequential methotrexate and S-FU combined with adriamycin in advanced measurable gastric cancer.J Clirr OncoZ1986,4,1799-1803. Wils JA, Klein HO, Wagener DJTh, er al. Sequential high-dose methotrexate and 5-fluorouracil combined with doxorubicin-a step ahead in the treatment of advanced gastric cancer: a trial of the European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group.3 Clin Oncoll991,9,827-83 1.
Correspondence to J. Wils. J. Wils is at Laurentius Hospital, Roermond; and H.O. Klein is at the Medizinische Universitats Klinik, Koln, Germany. Received and accepted 9 Dec. 1991.
Letters
EurJ Cancer, Vol. 28A, No. 617, p. 1299,199Z. Pnnred in GreatB&am 091%1947192$S.W + 0.00 0 1992 I’ergamon Press Ltd
Eur3 Cancer, VP/. Z8A, No. 617, p. 1299, 1992. Pnnud I” GrearBnratn G96&1947l92$5.00 i 0.00 0 1992 Pegama l’ress Ltd
Prolonged Thrombocytopenia After Procarbazine “Overdose” M. Hadjiyanni,
K. Valianatou, and B. Seitanidis
M. Tsilianos
MMAF for Advanced Gastric Cancer J. Wils and H.O. Klein ANDERSONet al.
report a phase II study with MMAF combination chemotherapy in 65 patients with advanced gastric cancer [ 11. MMAF is sequential high-dose methotrexate and 5-fluorouTHE MAJORtoxicity of procarbazine is dose-related reversible racil(5-FU) on day 1 with leucovorin rescue starting on day 2 haemopoietic suppression with leukopenia and thrombocytoand doxorubicin plus mitomycin on day 14. In fact, this is the penia in a significant percentage of the patients when it is given FAMTX regimen with additional mitomycin, 4 mg/m2. They at maximum dose of 3 mg/kg for 14 days [ 1, 21. achieved a response rate of 29%, including 6% with a complete We describe a patient with Hodgkin’s disease who received response and a median survival of 7 months without major procarbazine for 25 days (150 mg daily) and who developed toxicity. prolonged thrombocytopenia. These results are not different from those reported by the A 29-year-old male with stage IIIA lymphocyte predominance EORTC Gastrointestinal Tract Group in a multi-institutional Hodgkin’s disease started MOPP in July 1985 and inadvertantly phase II study with FAMTX (33% response rate and 6 months continued 150 mg procarbazine daily for 25 days. His blood median survival in 66 patients), with the exception of toxicity count remained normal, although the platelet count fell from which was higher in the EORTC study, mostly due to non230 x lo911pretreatment to 140 x lo9 post-treatment. adherence to the protocol [2]. A second course of full dosage MOPP was started on 9 August In a subsequent phase III study, the EORTC Gastrointestinal 1985. When he returned for the third cycle the platelet count Tract Group compared FAMTX with FAM in 213 patients and was 79 x 109/1. Chemotherapy was discontinued after the first found the FAMTX regimen to yield a significantly better week because of thrombocytopenia which persisted for the response rate and survival [3]. An updated survival comparison subsequent 4 years with platelet counts ranging from 20 x 109/1 in this study shows a median survival of 44 weeks for FAMTX to 30 x 109/1.A bone marrow aspiration, 20 days after chemoand of 29 weeks for FAM (P = 0.002). No imbalance between therapy, showed reduced cellularity with some megaloblastoid the groups could be detected in a Cox regression model. changes in the erythroblasts, a shift to the left in the granulocyte Therefore, we question the conclusion by Anderson et al. that series and megakaryocytes almost absent. MMAF did not improve the response or survival compared with No further chemotherapy was given. Radiotherapy was given FAM. The authors did not compare their regimen with FAM to the mediastinum where the main bulk of his disease was. He and no particular conclusion can be drawn from comparison received 18.5 Gy and discontinued treatment against medical with other phase II studies. We feel that MMAF as defined by advice. At that time haemoglobin was 10.8 gidl, white cells Anderson et al. is not essentially different from FAMTX, which were 4.5 x lo911 with normal differential, and platelets were is clearly superior to FAM. FAM should no longer be advocated 27 x 10’11.The platelet count started to recover in early 1989 for advanced gastric cancer. and by April 1991 the count was 350 x 10911.The patient remains in complete remission. The likely explanation for the patient’s thrombocytopenia is the protracted treatment with procarbazine with depletion of marrow reserves and suppression of committed megacaryocytic Anderson H, Scarffe JH, Ranson M, et al. MMAF for advanced stem cells. Selective toxicity of megakaryocytes to procarbazine gastric cancer. EurJ Cancer 1991,27,1234-1238. Wils, J, Bleiberg H, Dalesio 0, et al. An EORTC gastrointestinal has not been reported previously.
1. Henry MC, Marlow M. Preclinical toxicologicstudy of procarbazine (NSC-77213).CancerChem Rep 1973,4,97-102. 2. Stolinsky DC, Solomon J, Pugh RI’. Procarbazine HCL in Hodgkin’s
disease, reticulum cell sarcoma and lymphosarcoma. Cancer, 1970, 26,9&t-990.
Correspondence to B. Seitanides. The authors are at the Department of Clinical Haematology, Metaxas Memorial Hospital of Piraeus, 5 1 Botassi str., 185 37 Piraeus, Greece. Received 2 Dec. 1991; accepted 13 Dec. 1991.
group evaluation of the combination of sequential methotrexate and S-FU combined with adriamycin in advanced measurable gastric cancer.J Clirr OncoZ1986,4,1799-1803. Wils JA, Klein HO, Wagener DJTh, er al. Sequential high-dose methotrexate and 5-fluorouracil combined with doxorubicin-a step ahead in the treatment of advanced gastric cancer: a trial of the European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group.3 Clin Oncoll991,9,827-83 1.
Correspondence to J. Wils. J. Wils is at Laurentius Hospital, Roermond; and H.O. Klein is at the Medizinische Universitats Klinik, Koln, Germany. Received and accepted 9 Dec. 1991.
