Chemotherapy for small cell lung cancer: Induction and reinduction with voca

1
S36 disease. There was partial remission, six with doxorubicin, seven with epirubicin (one death in each group), and no response in five (doxoru- bicin; two deaths) and seven (epirubicin; five deaths). Toxicity was greater during and after cyclophosphamide and etoposide than during and after vincristine with either doxorubicin or epirubicin. Substitution of epirubicin for doxorubicin appeared not to offer any advantage in reduction in toxicity in the treatment of small cell lung cancer as used in this series. The low complete remission rate, the relatively high proportion of non-responders and the low incidence of serious leu- copenia indicates that the therapeutic regimen used was sub-optimal. It is suggested that this may bc because the treatment schedule was every four weeks instead of the more usual three-weekly treatments and the lack of cardiac toxicity may be because no patients received more than 200 mg/m2. It is concluded therefore that it would be worth including epirubicin into a more intensive treatment protocol, using a higher total dose and scheduling. the treatment every 21 davs. First-line chemotherapy rechallenge after relapse in small cell lung cancer. Vincent M, Evans B, Smith I. Lung Unit, Royal Mars&n Hospital. Sutton. Cancer Chemother Pharmacol 1988;21:45-8. Response to second-line therapy in relapsing patients with small cell lungcarcinoma(SCLC) isoftenclaitned tobeevidenceinfavourofnon- cross resistance. Fifteen patients with SCLC who had relapsed off treatment after responding to initial first-line chemotherapy were re- treated with the same regimen at relapse. Ten (67%) achieved a further partial response. Median response duration was only 3 months (range 2- 4 months), but similar poor results have been reported for most studies using second-line chemotherapy. Relapse in SCLC does not necessarily imply complete clinical resistance to first-line chemotherapy, and strict clinical criteria are required to demonstrate true non-cross resistance. A randomized comparative trial of sequential versus alternating cyclophosphamide, doxorubicin, and cisplatin and mitomycin, lomustine, and methotrexate in metastatic non-small-cell lung can- cer. Eagan RT, Frytak S, Richardson RL et al. Division of Medical Oncol- ogy, Medical Research Statistics,Division of Thoracic Diseases, Mayo Clinic, Rochester, MN55905. J Clin Oncol 1988:6:5-8. One hundred eight eligible patients with advanced, metastatic non- small-cell lung cancer (NSCLC) were randomized to treatment with either cyclophosphamide, doxorubicin, andcisplatin (CAP) followed by mitomycin, lomustine, and methotrexate (MCM) on progression (se- quential, 54 patients) or to CAP alternating with MCM (alternating, 54 patients). The regression rate (30%) was identical for both treatments. In addition, there were no statistically significant differences noted between treatments for regression duration (6.9 months v 7.6 months), time to progression (2.1 months v 4.4 months), or overall survival (5.5 months v 6.9 months). The lack of advantage for the theoretically superior alternating approach was probably due to a combination of relative ineffectiveness of each treatment and lack of complete non- cross resistance. Sensitivity of human non-small cell lung cancer xenografts to cyclophosphamide and cisplatin. Mattem J, Wayss K, Volm M. German Cancer Research Center, Institute of Experimental Pathology, D-6900 Heidelberg. In Vivo 1987;1:23-6. In order to establish the usefulness of the nude-mouse human tumour xenograft system as a predictive screen for antineoplastic agents, the antitumour activity of cyclophosphamide (CTX) and cisplatin (DDP), two clinically active drugs, was tested against a panel of I4 human non- small cell lung tumour xenografts and the experimental results were compared with the clinical results reported in the literature. The poor clinical response of non-small cell tumours was reflected in the lack of response of the xenograft tumours to these two agents. Phase I/II study of recombinant human granulocyte colony-stimu- lating factor in patients receiving intensive chemotherapy for small cell lung cancer. Bronchud MH, Scarffe JH, Thatcher N et al. Cancer Research Cam- paign Department of Medical Oncology, Paterson Institute for Cancer Research, Manchester M20 9BX. Br J Cancer 1987;56:809-13. Twelve patients with advanced small cell carcinoma of the bronchus were treated by continuous infusion of recombinant human granulocyte colony-stimulating factor (rhG-CSF) at the following dose levels: 1 ?? g, 5 ?? g, 10 ?? g, 20 ?? g and 40 ?? gkg-’ day-r for 5 days. No toxicities resulted from the treatment and in all 12 patients the number of peripheral neuuophils increased rapidly to a maximum of 100 x lOgI-’ at 10 ?? gkg day-‘ . The neutrophils were shown to be functionally normal in tests of their mobility and bactericidal activity. During the phase II part of the study thepatients weretreatedbyacombinationofintravenousadriamy- tin 50 mg m-*, ifosfamide 5 g m-* by i.v. infusion with mesna 8 g m20n day 1, and etoposide 120 mg m-z on days 1.2 and 3 also intravenously. The chemotherapy regime was repeated every 3 weeks. rhG-CSF was given toeachpatientfor 14daysonaltematecyclesofchemotherapyand reduced the period of absolute neutropenia considerably (median of 80%),witharetumtonormal,orabovenormal,neuuophilcountswithin 2 weeks after day 1 of chemotherapy. Six severe infective episodes were observed during the cycles of chemotherapy which did not include rhG- CSF, while no infective episodes occurred when patients were treated with rhG-CSF. These results demonstrate the utility of rhG-CSF in restoring functional neutrophils to patients undergoing intensive che- motherapy. Chemotherapy for small cell lung cancer: Induction and reinduc- tion with voca. Stuart-Harris R, Raghavan D, Fox RM et al. Ludwiglnstitutefor Cancer Research, University of Sydney, Sydney, NSW. Aust New Zealand J Med 1987;17:279-82. Sixty-five patients with small cell lung cancer were treated with VP16, vincristinc, cyclophosphamide, and doxorubicin (VOCA) intra- venously at three-week intervals. Patients with limited disease received four cycles with responders receiving radiation to the primary site and prophylactic cranial irradiation. Patients with extensive disease re- ceived chemotherapy only. Of 59 patients cvaluablc for chemotherapy rcsponsc,eight(l4%)achievedcompleteremission~d3O(5l%)partial remission. Major side-cffccts included myelosuppression, alopecia, nausea, and vomiting. Reinduction with VOCA at rclapsc yielded objective or subjective response in four of seven patients. This regimen is active in small cell lung cancer and was well tolerated by patients. Reinduction of response was possible in a small number of patients rctrcate and may provide useful palliation for those when treatment is discontinued. Mitomycin C, vinblastine and cisplatin combination chemotherapy in the treatment of advanced non-small cell lung cancer. NomuraF,ShimokataK,SaitoH,SakaiS,WatanabeA,SakaH.Depart- men1 ofMedicine. Japanese Red Cross Nagoya First Hospital, Nagoya.

Transcript of Chemotherapy for small cell lung cancer: Induction and reinduction with voca

S36

disease. There was partial remission, six with doxorubicin, seven with epirubicin (one death in each group), and no response in five (doxoru- bicin; two deaths) and seven (epirubicin; five deaths). Toxicity was greater during and after cyclophosphamide and etoposide than during and after vincristine with either doxorubicin or epirubicin. Substitution of epirubicin for doxorubicin appeared not to offer any advantage in reduction in toxicity in the treatment of small cell lung cancer as used in this series. The low complete remission rate, the relatively high proportion of non-responders and the low incidence of serious leu- copenia indicates that the therapeutic regimen used was sub-optimal. It is suggested that this may bc because the treatment schedule was every four weeks instead of the more usual three-weekly treatments and the lack of cardiac toxicity may be because no patients received more than 200 mg/m2. It is concluded therefore that it would be worth including epirubicin into a more intensive treatment protocol, using a higher total dose and scheduling. the treatment every 21 davs.

First-line chemotherapy rechallenge after relapse in small cell lung cancer. Vincent M, Evans B, Smith I. Lung Unit, Royal Mars&n Hospital. Sutton. Cancer Chemother Pharmacol 1988;21:45-8.

Response to second-line therapy in relapsing patients with small cell lungcarcinoma(SCLC) isoftenclaitned tobeevidenceinfavourofnon- cross resistance. Fifteen patients with SCLC who had relapsed off treatment after responding to initial first-line chemotherapy were re- treated with the same regimen at relapse. Ten (67%) achieved a further partial response. Median response duration was only 3 months (range 2- 4 months), but similar poor results have been reported for most studies using second-line chemotherapy. Relapse in SCLC does not necessarily imply complete clinical resistance to first-line chemotherapy, and strict clinical criteria are required to demonstrate true non-cross resistance.

A randomized comparative trial of sequential versus alternating cyclophosphamide, doxorubicin, and cisplatin and mitomycin, lomustine, and methotrexate in metastatic non-small-cell lung can- cer. Eagan RT, Frytak S, Richardson RL et al. Division of Medical Oncol- ogy, Medical Research Statistics, Division of Thoracic Diseases, Mayo Clinic, Rochester, MN55905. J Clin Oncol 1988:6:5-8.

One hundred eight eligible patients with advanced, metastatic non- small-cell lung cancer (NSCLC) were randomized to treatment with either cyclophosphamide, doxorubicin, andcisplatin (CAP) followed by mitomycin, lomustine, and methotrexate (MCM) on progression (se- quential, 54 patients) or to CAP alternating with MCM (alternating, 54 patients). The regression rate (30%) was identical for both treatments. In addition, there were no statistically significant differences noted between treatments for regression duration (6.9 months v 7.6 months), time to progression (2.1 months v 4.4 months), or overall survival (5.5 months v 6.9 months). The lack of advantage for the theoretically superior alternating approach was probably due to a combination of relative ineffectiveness of each treatment and lack of complete non- cross resistance.

Sensitivity of human non-small cell lung cancer xenografts to cyclophosphamide and cisplatin. Mattem J, Wayss K, Volm M. German Cancer Research Center, Institute of Experimental Pathology, D-6900 Heidelberg. In Vivo 1987;1:23-6.

In order to establish the usefulness of the nude-mouse human tumour xenograft system as a predictive screen for antineoplastic agents, the antitumour activity of cyclophosphamide (CTX) and cisplatin (DDP), two clinically active drugs, was tested against a panel of I4 human non- small cell lung tumour xenografts and the experimental results were compared with the clinical results reported in the literature. The poor clinical response of non-small cell tumours was reflected in the lack of response of the xenograft tumours to these two agents. Phase I/II study of recombinant human granulocyte colony-stimu-

lating factor in patients receiving intensive chemotherapy for small cell lung cancer. Bronchud MH, Scarffe JH, Thatcher N et al. Cancer Research Cam- paign Department of Medical Oncology, Paterson Institute for Cancer Research, Manchester M20 9BX. Br J Cancer 1987;56:809-13.

Twelve patients with advanced small cell carcinoma of the bronchus were treated by continuous infusion of recombinant human granulocyte colony-stimulating factor (rhG-CSF) at the following dose levels: 1 ??g, 5 ??g, 10 ??g, 20 ??g and 40 ??gkg-’ day-r for 5 days. No toxicities resulted from the treatment and in all 12 patients the number of peripheral neuuophils increased rapidly to a maximum of 100 x lOgI-’ at 10 ??gkg ’ day-‘. The neutrophils were shown to be functionally normal in tests of their mobility and bactericidal activity. During the phase II part of the study thepatients weretreatedbyacombinationofintravenousadriamy- tin 50 mg m-*, ifosfamide 5 g m-* by i.v. infusion with mesna 8 g m20n day 1, and etoposide 120 mg m-z on days 1.2 and 3 also intravenously. The chemotherapy regime was repeated every 3 weeks. rhG-CSF was given toeachpatientfor 14daysonaltematecyclesofchemotherapyand reduced the period of absolute neutropenia considerably (median of 80%),witharetumtonormal,orabovenormal,neuuophilcountswithin 2 weeks after day 1 of chemotherapy. Six severe infective episodes were observed during the cycles of chemotherapy which did not include rhG- CSF, while no infective episodes occurred when patients were treated with rhG-CSF. These results demonstrate the utility of rhG-CSF in restoring functional neutrophils to patients undergoing intensive che- motherapy.

Chemotherapy for small cell lung cancer: Induction and reinduc- tion with voca. Stuart-Harris R, Raghavan D, Fox RM et al. Ludwiglnstitutefor Cancer Research, University of Sydney, Sydney, NSW. Aust New Zealand J Med 1987;17:279-82.

Sixty-five patients with small cell lung cancer were treated with VP16, vincristinc, cyclophosphamide, and doxorubicin (VOCA) intra- venously at three-week intervals. Patients with limited disease received four cycles with responders receiving radiation to the primary site and prophylactic cranial irradiation. Patients with extensive disease re- ceived chemotherapy only. Of 59 patients cvaluablc for chemotherapy rcsponsc,eight(l4%)achievedcompleteremission~d3O(5l%)partial remission. Major side-cffccts included myelosuppression, alopecia, nausea, and vomiting. Reinduction with VOCA at rclapsc yielded objective or subjective response in four of seven patients. This regimen is active in small cell lung cancer and was well tolerated by patients. Reinduction of response was possible in a small number of patients rctrcate and may provide useful palliation for those when treatment is discontinued.

Mitomycin C, vinblastine and cisplatin combination chemotherapy in the treatment of advanced non-small cell lung cancer. NomuraF,ShimokataK,SaitoH,SakaiS,WatanabeA,SakaH.Depart- men1 ofMedicine. Japanese Red Cross Nagoya First Hospital, Nagoya.