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THROMBOTIC COMPLICATIONS IN PATIENTS WITH ADVANCED PROSTATIC CANCER TREATED WITH CHEMOTHERAPY
159 We have
seen a case
of
gastric carcinoma
that simulated
H.M.R.6 Erythrocytic, granulocytic, and platelet phagocytosis
by bone-marrow histiocytes were observed in a patient with fever, jaundice, hepatomegaly, and anaemia. Necropsy revealed a gastric adenocarcinoma with metastasis to the liver. There was no evidence of a diffuse histiocytic proliferation. All these observations suggest that
H.M.R.
should be
care-
fully investigated for viral, bacterial, parasitic, and carcinomatous aetiologies. Perhaps H.M.R. should be divided into primary and secondary causes. Department of Laboratory Medicine, National Naval Medical Center, Bethesda, Maryland 20014, U.S.A.
H. R. SCHUMACHER S. A. STASS
THROMBOTIC COMPLICATIONS IN PATIENTS WITH ADVANCED PROSTATIC CANCER TREATED WITH CHEMOTHERAPY
SIR--Patients with prostatic cancer are at high risk of thromboembolic complications for several reasons, including decreased mobility due to advanced age or disease, concomitant cardiovascular problems, the malignant disease itself,’1 and, most important, the administration of oestrogens.23 Traditional treatment for stage-D prostate carcinoma includes hormonal therapy, orchidectomy, palliative radiotherapy, and analgesia. Lately cytotoxic drugs have been tried, without success. During a trial of chemotherapy we noted a high frequency of thrombotic complications in patients treated without hormones. TUMOUR RESPONSE TO CHEMOTHERAPY AND THROMBOEMBOLIC COMPLICATIONS IN
21
MEN WITH PROSTATIC CANCER
’ See text.
+ D.v.T.=deep-vein thrombosis. i.v.c.=inferior
vena cava
obstruction.
23 men with stage-D prostatic cancer were treated with single agent or combination chemotherapy for approximately twenty months. In 17 hormone treatment had been tried but this failed to control the disease. No hormonal therapy was used during the trial. The most commonly used combination
cyclophosphamide, doxorubicin, and methotrexate (C.A.M.). Patient 2 received 5-fluorouracil but after disease progression was assigned to C.A.M. In patients 5 and 11 doxorubicin was omitted because of cardiac problems. Patients 13 and 20 received a combination of cis-platinum, hydroxyurea, and 5-fluorouracil after disease progression on C.A.M. 2 patients were excluded from study; 1 had three malignant diseases simultaneously and 1 was lost to follow-up. The response to
was
treatment was scored as:
Complete response (CR)-No clinically detectable tumour. Partial response (PR)-Reduction by at least 50% of a measurable lesion. Stabilisation of disease (SD)-Decrease of less than 50% or an increase of less than 25% over the original tumour measurements. Subjective response (SR)-Patient felt better and significant pain relief was obtained. No response (NR)-Unchanged tumour measurements. Progression of disease (PD)-Increase by 25% or greater of the original measurements or significant deterioration of symptoms and performance status. Performance status was evaluated by standard Eastern Cooperative Oncology Group criteria (0-4, with 0 being the best status).
complications were documented by venogram, vena cava contrast study, and/or cliniinferior Doppler scan, cally. The trial was terminated in June, 1978, and retrospective analysis of the charts was started in July, 1978. Of the 17 patients who had received oestrogen therapy before chemotherapy 11 had shown subjective responses to oestrogen treatment. While on hormones, patients 9 and 19 had deep-vein thrombosis and patient 1 had a pulmonary embolism. All responded well to anticoagulant therapy. No patient began chemotherapy with a performance status greater than 2. 7 patients did not respond to chemotherapy and 4 of them had thrombotic complications (see table). 3 of these 4 patients had discontinued oestrogens at least three weeks before thrombosis and the fourth never received hormones. A fifth patient who was not taking oestrogens had thrombotic complications while his disease was responding to chemotherapy. Thus, to our surprise, 5 of 21 patients (24%) had thromboembolic complications while on chemotherapy alone. None had pulmonary embolism, and all responded to conventional anticoagulation. 4 of the patients with thrombotic complications had manifestations of further disease progression at the same time. 10 of the 21 patients ultimately showed tumour progression and were taken off study or assigned to another protocol. No patient had signs of congestive heart-failure. The Veterans Administration study23 of hormones in the treatment of prostatic cancer showed a definite relation between mortality from cardiovascular complications and oestrogen dose. Morales et awl. reported increased cardiovascular morbidity in a series of 154 patients: for a diethylstilbcestrol-treated group the frequency was 22.2% versus 9.3% for chlorotrianisene and 9.5% for ethinyloestradiol. The mortality figures showed no significant difference between the three groups. We know of no report of the incidence of thromboembolism in untreated patients with advanced prostatic carcinoma, and no report describes thromboembolic morbidity in patients treated with chemotherapy. 24% of our patients had some form of thrombosis usually associated with disease progression. This small series points to an association between disease activity and the development of thrombotic complications. A relation between chemotherapy and thrombosis, as a result of tumour lysis, is highly unlikely; Thrombotic
the
complication occurred in 4 patients failing on chemoand in only 1 responder. If this association were con-
therapy firmed cancer
6. James, L. P., Stass, S. A., Peterson, V., Schumacher, H. R. Am. J. clin. Path. (in the press). 1. Lieberman, J, S., Borrero, J., Urdaneta, E., Wright, I. S. J. Am. med. Ass.
1961, 177, 542. 2. Bailar, J. C., Byar, D. P. and the Veterans Administration Cooperative Urological Research Group. Cancer, 1970, 26, 257. 3. Blackard, C. E. Cancer Chemother. Rep. 1975, 59, 225.
trial of prophylactic might be indicated. a
Section of Medical
Oncology, University Hospital, Boston, Massachusetts 02118, U.S.A. 4.
anticoagulation
in
prostatic
BASIL S. KASIMIS ALEXANDER S. D. SPIERS
Morales, A., Pujari, B. Can. med. Ass. J. 1975, 113, 865.
seen a case
of
gastric carcinoma
that simulated
H.M.R.6 Erythrocytic, granulocytic, and platelet phagocytosis
by bone-marrow histiocytes were observed in a patient with fever, jaundice, hepatomegaly, and anaemia. Necropsy revealed a gastric adenocarcinoma with metastasis to the liver. There was no evidence of a diffuse histiocytic proliferation. All these observations suggest that
H.M.R.
should be
care-
fully investigated for viral, bacterial, parasitic, and carcinomatous aetiologies. Perhaps H.M.R. should be divided into primary and secondary causes. Department of Laboratory Medicine, National Naval Medical Center, Bethesda, Maryland 20014, U.S.A.
H. R. SCHUMACHER S. A. STASS
THROMBOTIC COMPLICATIONS IN PATIENTS WITH ADVANCED PROSTATIC CANCER TREATED WITH CHEMOTHERAPY
SIR--Patients with prostatic cancer are at high risk of thromboembolic complications for several reasons, including decreased mobility due to advanced age or disease, concomitant cardiovascular problems, the malignant disease itself,’1 and, most important, the administration of oestrogens.23 Traditional treatment for stage-D prostate carcinoma includes hormonal therapy, orchidectomy, palliative radiotherapy, and analgesia. Lately cytotoxic drugs have been tried, without success. During a trial of chemotherapy we noted a high frequency of thrombotic complications in patients treated without hormones. TUMOUR RESPONSE TO CHEMOTHERAPY AND THROMBOEMBOLIC COMPLICATIONS IN
21
MEN WITH PROSTATIC CANCER
’ See text.
+ D.v.T.=deep-vein thrombosis. i.v.c.=inferior
vena cava
obstruction.
23 men with stage-D prostatic cancer were treated with single agent or combination chemotherapy for approximately twenty months. In 17 hormone treatment had been tried but this failed to control the disease. No hormonal therapy was used during the trial. The most commonly used combination
cyclophosphamide, doxorubicin, and methotrexate (C.A.M.). Patient 2 received 5-fluorouracil but after disease progression was assigned to C.A.M. In patients 5 and 11 doxorubicin was omitted because of cardiac problems. Patients 13 and 20 received a combination of cis-platinum, hydroxyurea, and 5-fluorouracil after disease progression on C.A.M. 2 patients were excluded from study; 1 had three malignant diseases simultaneously and 1 was lost to follow-up. The response to
was
treatment was scored as:
Complete response (CR)-No clinically detectable tumour. Partial response (PR)-Reduction by at least 50% of a measurable lesion. Stabilisation of disease (SD)-Decrease of less than 50% or an increase of less than 25% over the original tumour measurements. Subjective response (SR)-Patient felt better and significant pain relief was obtained. No response (NR)-Unchanged tumour measurements. Progression of disease (PD)-Increase by 25% or greater of the original measurements or significant deterioration of symptoms and performance status. Performance status was evaluated by standard Eastern Cooperative Oncology Group criteria (0-4, with 0 being the best status).
complications were documented by venogram, vena cava contrast study, and/or cliniinferior Doppler scan, cally. The trial was terminated in June, 1978, and retrospective analysis of the charts was started in July, 1978. Of the 17 patients who had received oestrogen therapy before chemotherapy 11 had shown subjective responses to oestrogen treatment. While on hormones, patients 9 and 19 had deep-vein thrombosis and patient 1 had a pulmonary embolism. All responded well to anticoagulant therapy. No patient began chemotherapy with a performance status greater than 2. 7 patients did not respond to chemotherapy and 4 of them had thrombotic complications (see table). 3 of these 4 patients had discontinued oestrogens at least three weeks before thrombosis and the fourth never received hormones. A fifth patient who was not taking oestrogens had thrombotic complications while his disease was responding to chemotherapy. Thus, to our surprise, 5 of 21 patients (24%) had thromboembolic complications while on chemotherapy alone. None had pulmonary embolism, and all responded to conventional anticoagulation. 4 of the patients with thrombotic complications had manifestations of further disease progression at the same time. 10 of the 21 patients ultimately showed tumour progression and were taken off study or assigned to another protocol. No patient had signs of congestive heart-failure. The Veterans Administration study23 of hormones in the treatment of prostatic cancer showed a definite relation between mortality from cardiovascular complications and oestrogen dose. Morales et awl. reported increased cardiovascular morbidity in a series of 154 patients: for a diethylstilbcestrol-treated group the frequency was 22.2% versus 9.3% for chlorotrianisene and 9.5% for ethinyloestradiol. The mortality figures showed no significant difference between the three groups. We know of no report of the incidence of thromboembolism in untreated patients with advanced prostatic carcinoma, and no report describes thromboembolic morbidity in patients treated with chemotherapy. 24% of our patients had some form of thrombosis usually associated with disease progression. This small series points to an association between disease activity and the development of thrombotic complications. A relation between chemotherapy and thrombosis, as a result of tumour lysis, is highly unlikely; Thrombotic
the
complication occurred in 4 patients failing on chemoand in only 1 responder. If this association were con-
therapy firmed cancer
6. James, L. P., Stass, S. A., Peterson, V., Schumacher, H. R. Am. J. clin. Path. (in the press). 1. Lieberman, J, S., Borrero, J., Urdaneta, E., Wright, I. S. J. Am. med. Ass.
1961, 177, 542. 2. Bailar, J. C., Byar, D. P. and the Veterans Administration Cooperative Urological Research Group. Cancer, 1970, 26, 257. 3. Blackard, C. E. Cancer Chemother. Rep. 1975, 59, 225.
trial of prophylactic might be indicated. a
Section of Medical
Oncology, University Hospital, Boston, Massachusetts 02118, U.S.A. 4.
anticoagulation
in
prostatic
BASIL S. KASIMIS ALEXANDER S. D. SPIERS
Morales, A., Pujari, B. Can. med. Ass. J. 1975, 113, 865.