A Phase II Study on Lonidamine Combined with Cisplatin and Etoposide in the Treatment of Advanced Non-Small Cell Bronchogenic Carcinoma (NSCBC)

Lelli, G.; Guaraldi, M.; Canova, Nadia; Casadio, M; Pannuti, F

doi:10.1080/1120009x.1990.11739053

Journal of Chemotherapy

1990

DOI: 10.1080/1120009x.1990.11739053

|View full text |Cite

A Phase II Study on Lonidamine Combined with Cisplatin and Etoposide in the Treatment of Advanced Non-Small Cell Bronchogenic Carcinoma (NSCBC)

G. Lelli¹,

M. Guaraldi²,

Nadia Canova³

et al.

Abstract: A group of 28 patients with advanced non-small cell bronchogenic carcinoma (NSCBC) entered a phase II study on cisplatin (60 mg/m2, day 1) plus etoposide 120 mg/m2, day 1 to 3), every 3 weeks, in combination with lonidamine (150 mg p.o. t.i.d. continuously from day 1). Seven out of twenty-seven (26%) evaluable patients obtained a partial remission (median duration 22 weeks, range 7-47). Although the side effects were mild, three patients stopped the therapy because of them. Median survival was 14 months, range… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

1993

1996

Publication Types

Select...

Article3

Relationship

Self Cite0

Independent3

Authors

Journals

Cited by 3 publications

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

A phase II study of methotrexate, doxorubicin, cyclophosphamide, and lomustine chemotherapy and lonidamine in advanced non-small cell lung cancer

Buccheri¹,

Ferrigno²,

Rosso³

1993

Cancer

View full text Add to dashboard Cite

Background. Combination chemotherapy with conventional antiproliferative drugs is becoming the treatment of choice for patients with advanced non‐small cell lung cancer (NSCLC), a good performance status, and no major clinical contraindications. Lonidamine (LND), a new drug with an innovative mechanism of action, might potentiate anticancer activity, without increasing toxicity. Methods. In a Phase II study, 46 patients with advanced NSCLC were assigned to receive chemotherapy with the methotrexate, doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (MACC) regimen, as originally described, plus LND, 150 mg orally, three times per day. Treatment was continued until progression of disease, occurrence of unacceptable toxic effects, or refusal by the patient (the median duration of MACC treatment was 6 weeks; 7 weeks for LND). Results. For the whole group of patients, actual dose intensities (DI) of MACC and LND were 95% and 67% of those projected (median values), respectively. There was a negative correlation between duration of chemotherapy and the DI of MACC reached in each patient. On the contrary, there was no correlation between the duration of treatment with LND and its DI. The DI of LND and MACC were not correlated with each other. In all, seven objective responses (only partial responses) were observed. The overall median survival time was 42 weeks (confidence limits [CL], 20–52). The median survival length of patients receiving the full dose of LND (450 mg daily for at least 1 week) was 46 weeks (CL, 28–67), as compared with the median survival of 19 weeks (lower CL, 9 weeks) for the remaining patients; this difference was statistically significant (P ± 0.05, Breslow test). Toxic effects were as expected with the use of MACC. They were mainly gastrointestinal (any grade of toxicity occurring in 64% of the patients), hematologic (anemia, 44%; leukopenia, 36%; thrombocytopenia, 8%), oral (25%), renal (14%), and cardiac (11%). There was only one treatment‐related death, from myocardial infarction and neutropenic sepsis. Uncommon side effects, which were attributed to LND, were mild to moderate and reversible; they included myalgia (26%), asthenia (15%), testicle pain (11%), visual problems (7%), and gastric intolerance (7%). Conclusions. MACC plus LND is a moderately active regimen in advanced NSCLC, with foreseeable and reversible toxic effects of low–medium grade. Potential enhancements of antitumor activity and possible host survival benefits may be expected by the addition of LND to MACC, but a Phase III study must be performed to identify them.

show abstract

A phase II study of methotrexate, doxorubicin, cyclophosphamide, and lomustine chemotherapy and lonidamine in advanced non-small cell lung cancer

Buccheri¹,

Ferrigno²,

Rosso³

1993

Cancer

View full text Add to dashboard Cite

show abstract

Efficacy of lonidamine combined with different DNA-damaging agents in the treatment of the MX-1 tumor xenograft

Pratesi

Cesare

Zunino

1996

Cancer Chemotherapy and Pharmacology

View full text Add to dashboard Cite

Lonidamine is an antitumor agent with a peculiar mechanism of action, since it differentially impairs the energy metabolism of normal and neoplastic cells. We investigated the effects of lonidamine on the activity of DNA-damaging antitumor agents against the MX-1 human breast carcinoma xenograft. Athymic mice bearing measurable s.c. tumors were treated by a single injection of doxorubicin (i.v.), cyclophosphamide (i.v.), or cisplatin (i.p.) followed by repeated daily injections of lonidamine (i.p. or p.o.). A potentiation of the activity of all these DNA-damaging drugs was achieved when each was given in combination with lonidamine, but for doxorubicin and cyclophosphamide the increase in antitumor activity paralleled the increase in lethal toxicity. In contrast, a therapeutic advantage of the combination was achieved for cisplatin and lonidamine as compared with cisplatin alone. Indeed, 6 mg/kg of cisplatin plus lonidamine cured all tumors, whereas the maximum tolerated dose of cisplatin alone (12 mg/kg) cured only six of eight tumors. In addition, the study indicated that the duration of lonidamine administration after injection of the cytotoxic drug influenced the tumor response and that prolonged treatment resulted in greater efficacy. These results document the ability of lonidamine to modulate the pharmacological activity of DNA-damaging drugs, thus suggesting that lonidamine may be a clinically useful cisplatin modulator.

show abstract

A randomised trial of MACC chemotherapy with or without lonidamine in advanced non-small cell lung cancer

Buccheri

Ferrigno

1994

European Journal of Cancer

View full text Add to dashboard Cite

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

A Phase II Study on Lonidamine Combined with Cisplatin and Etoposide in the Treatment of Advanced Non-Small Cell Bronchogenic Carcinoma (NSCBC)

Cited by 3 publications

References 10 publications

A phase II study of methotrexate, doxorubicin, cyclophosphamide, and lomustine chemotherapy and lonidamine in advanced non-small cell lung cancer

A phase II study of methotrexate, doxorubicin, cyclophosphamide, and lomustine chemotherapy and lonidamine in advanced non-small cell lung cancer

Efficacy of lonidamine combined with different DNA-damaging agents in the treatment of the MX-1 tumor xenograft

A randomised trial of MACC chemotherapy with or without lonidamine in advanced non-small cell lung cancer

Contact Info

Product

Resources

About